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HACEK organisms

2025-05-07T13:46:44Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{short description|Group of bacteria}}
{{redirect|HACEK|the diacritical mark known as háček|Caron}}
The '''HACEK organisms''' are a group of [[fastidious organism|fastidious]] [[Gram-negative]] [[bacteria]] that are an unusual cause of [[infective endocarditis]], which is an inflammation of the heart due to bacterial infection.<ref name="Reclassification of HACEK organisms">{{cite journal|last1=Nørskov-Lauritsen|first1=N|title=Classification, identification, and clinical significance of haemophilus and aggregatibacter species with host specificity for humans|journal=Clinical Microbiology Reviews|date=Apr 2014|volume=27|issue=2|pages=214–40|pmid=24696434|pmc=3993099|doi=10.1128/CMR.00103-13}}</ref> HACEK is an abbreviation of the initials of the [[genera]] of this group of bacteria: ''[[Haemophilus]]'', ''[[Aggregatibacter]]'' (previously ''[[Actinobacillus]]''), ''[[Cardiobacterium]]'', ''[[Eikenella]]'', ''[[Kingella]]''.<ref name="Reclassification of HACEK organisms" /> The HACEK organisms are a normal part of the [[human microbiota]], living in the [[Mouth|oral]]-[[pharynx|pharyngeal]] region.<ref name="HACEK in kids">{{cite journal|last1=Feder HM|first1=Jr|last2=Roberts|first2=JC|last3=Salazar|first3=J|last4=Leopold|first4=HB|last5=Toro-Salazar|first5=O|title=HACEK endocarditis in infants and children: two cases and a literature review.|journal=The Pediatric Infectious Disease Journal|date=Jun 2003|volume=22|issue=6|pages=557–62|pmid=12799515|doi=10.1097/01.inf.0000069795.12338.cf|s2cid=3238233}}</ref>

The bacteria were originally grouped because they were thought to be a significant cause of infective endocarditis, but recent research has shown that they are rare and only responsible for 1.4–3.0% of all cases of this disease.<ref name="Reclassification of HACEK organisms" />

==Organisms==
HACEK originally referred to ''[[Haemophilus parainfluenzae]]'', ''[[Haemophilus aphrophilus]]'', ''[[Actinobacillus actinomycetemcomitans]]'', ''[[Cardiobacterium hominis]]'', ''[[Eikenella corrodens]]'', and ''[[Kingella kingae]]''. However, taxonomic rearrangements have changed the A to ''[[Aggregatibacter]]'' species and the '''H''' to ''[[Haemophilus]]'' species to reflect the recategorization and novel identification of many of the species in these [[genera]].<ref name="Reclassification of HACEK organisms" /> Some reviews of medical literature on HACEK organisms use the older classification,<ref>{{cite journal|last1=Raza|first1=SS|last2=Sultan|first2=OW|last3=Sohail|first3=MR|title=Gram-negative bacterial endocarditis in adults: state-of-the-heart.|journal=Expert Review of Anti-infective Therapy|date=Aug 2010|volume=8|issue=8|pages=879–85|pmid=20695743|doi=10.1586/eri.10.76|s2cid=48457}}</ref> but recent papers are using the new classification.<ref>{{cite journal|last1=Chambers|first1=ST|last2=Murdoch|first2=D|last3=Morris|first3=A|last4=Holland|first4=D|last5=Pappas|first5=P|last6=Almela|first6=M|last7=Fernández-Hidalgo|first7=N|last8=Almirante|first8=B|last9=Bouza|first9=E|last10=Forno|first10=D|last11=del Rio|first11=A|last12=Hannan|first12=MM|last13=Harkness|first13=J|last14=Kanafani|first14=ZA|last15=Lalani|first15=T|last16=Lang|first16=S|last17=Raymond|first17=N|last18=Read|first18=K|last19=Vinogradova|first19=T|last20=Woods|first20=CW|last21=Wray|first21=D|last22=Corey|first22=GR|last23=Chu|first23=VH|last24=International Collaboration on Endocarditis Prospective Cohort Study|first24=Investigators|title=HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.|journal=PLOS ONE|date=2013|volume=8|issue=5|pages=e63181|pmid=23690995|doi=10.1371/journal.pone.0063181|pmc=3656887|bibcode=2013PLoSO...863181C|doi-access=free}}</ref><ref name="primary source on HACEK endocarditis"/><ref name="pmid 23682079"/>

A list of HACEK organisms:
*''[[Haemophilus]] ''species
**''[[Haemophilus haemolyticus]]''<ref name="pmid 23682079">{{cite journal|last1=Wassef|first1=N|last2=Rizkalla|first2=E|last3=Shaukat|first3=N|last4=Sluka|first4=M|title=HACEK-induced endocarditis|journal=BMJ Case Reports|date=May 15, 2013|volume=2013|pages=bcr2012007359|pmid=23682079|doi=10.1136/bcr-2012-007359|pmc=3670033}}</ref>
**''[[Haemophilus influenzae]]'': The incidence of endocarditis due to ''H. influenzae'' declined after the introduction of the [[Hib vaccine]].<ref name="Reclassification of HACEK organisms" />
**''[[Haemophilus parahaemolyticus]]''<ref name="pmid 23682079" />
**''[[Haemophilus parainfluenzae]]''<ref name="primary source on HACEK endocarditis"/>

*''[[Aggregatibacter]]''
**''[[Aggregatibacter actinomycetemcomitans]]'' (previously ''[[Actinobacillus actinomycetemcomitans]]'')
**''[[Aggregatibacter aphrophilus]]'' (previously ''[[Haemophilus aphrophilus]]'')
**''[[Aggregatibacter paraphrophilus]]'' (previously ''[[Haemophilus aphrophilus]]'')
**''[[Haemophilus segnis|Aggregatibacter segnis]]''

*''[[Cardiobacterium]]''
**''[[Cardiobacterium hominis]]'': This is the most common species in the genus ''Cardiobacterium''.
**''[[Cardiobacterium valvarum]]''

*''[[Eikenella]]''
**''[[Eikenella corrodens]]''<ref name="primary source on HACEK endocarditis">{{cite journal|last1=Sen Yew|first1=H|last2=Chambers|first2=ST|last3=Roberts|first3=SA|last4=Holland|first4=DJ|last5=Julian|first5=KA|last6=Raymond|first6=NJ|last7=Beardsley|first7=J|last8=Read|first8=KM|last9=Murdoch|first9=DR|title=Association between HACEK bacteraemia and endocarditis|journal=Journal of Medical Microbiology|date=Jun 2014|volume=63|issue=Pt 6|pages=892–5|pmid=24681996|doi=10.1099/jmm.0.070060-0|s2cid=206195338|doi-access=free}}</ref>

*''[[Kingella]]''
**''[[Kingella denitrificans]]''<ref name="primary source on HACEK endocarditis" />
**''[[Kingella kingae]]'': This is the most common species in the genus ''Kingella''.

==Presentation==
All of these organisms are part of the normal oropharyngeal flora, which grow slowly (up to 14 days), prefer a carbon dioxide–enriched atmosphere, and share an enhanced capacity to produce endocardial infections, especially in young children. Collectively, they account for 5–10% of cases of infective [[endocarditis]] involving native valves and are the most common Gram-negative cause of endocarditis among people who do not use drugs intravenously. They have been a frequent cause of culture-negative endocarditis. Culture-negative refers to an inability to produce a colony on regular agar plates because these bacteria are fastidious (require a specific nutrient).

In addition to valvular infections in the heart, they can also produce other infections, such as [[bacteremia]], [[abscess]], [[peritonitis]], [[otitis media]], [[conjunctivitis]], [[pneumonia]], [[arthritis]], [[osteomyelitis]], and [[Periodontitis|periodontal infections]].

==Treatment==
The treatment of choice for HACEK organisms in endocarditis is the third-generation [[cephalosporin]] and [[β-Lactam]] antibiotic [[ceftriaxone]]. [[Ampicillin]] (a [[penicillin]]), combined with low-dose [[gentamicin]] (an [[aminoglycoside]]) is another therapeutic option.<ref>[http://emedicine.medscape.com/article/218158-treatment], eMedicine, HACEK organism infection. June 2005.</ref>

==References==
{{reflist|2}}

{{Gram-negative proteobacterial diseases}}
{{Heart diseases}}

{{DEFAULTSORT:Hacek Endocarditis}}
[[Category:Bacteria]]
[[Category:Pathogenic bacteria]]

Brucella abortus

2025-05-07T13:45:09Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{Short description|Species of bacterium}}
{{Speciesbox
| image = Brucella spp.JPG
| image_caption = ''Brucella'' spp. are gram-negative in their staining morphology. ''Brucella'' spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 µm), and are seen mostly as single cells and appearing like "fine sand".
| taxon = Brucella abortus
| authority = (Schmidt, 1901) Meyer and Shaw, 1920
}}

'''''Brucella abortus''''' is a [[Gram-negative bacteria|Gram-negative]] [[bacterium]] in the family [[Brucellaceae]] and is one of the causative agents of [[brucellosis]]. The rod-shaped pathogen is classified under the domain Bacteria.<ref>{{Cite web |url= http://nih.gov/ |title= National Institutes of Health (NIH) |publisher= National Institutes of Health (NIH) |language= en |access-date= 2017-10-25 |archive-date= 2019-05-29 |archive-url= https://web.archive.org/web/20190529220121/https://www.nih.gov/ |url-status= dead }}</ref> The prokaryotic ''B. abortus'' is non-spore-forming, non-motile and aerobic.<ref>{{Cite news |url= http://cdc.gov/ |title= CDC Works 24/7 |date=2017-10-24 |agency= Centers for Disease Control and Prevention |access-date= 2017-10-25 |language=en-us}}</ref>

== Transmission ==
''Brucella abortus'' enters phagocytes that invade human and animal innate defenses which in turn, cause chronic disease in the host. The liver and [[spleen]] are the mainly affected areas of the body.<ref>{{Cite news |url= http://cdc.gov/ |title= CDC Works 24/7 |date=2017-10-24 |publisher= Centers for Disease Control and Prevention |access-date=2017-10-25|language=en-us}}</ref> Farm workers and veterinarians are the highest risk individuals for acquiring the disease due to their close proximity to the animals. Swine, goats, sheep, and cattle are a few of the reservoirs for the disease.<ref>{{Cite news |url= http://cdc.gov/|title=CDC Works 24/7|date=2017-10-24 |publisher= Centers for Disease Control and Prevention |access-date= 2017-10-25 |language=en-us}}</ref> ''B. abortus'' causes abortion and infertility in adult cattle and is a [[zoonosis]] which is present worldwide.<ref name="Dorneles 2015">{{cite journal |last1= Dorneles |first1=EM |last2=Sriranganathan |first2=N |last3=Lage |first3=AP |title= Recent advances in ''Brucella abortus'' vaccines. |journal= Veterinary Research |date=8 July 2015 |volume=46 |issue=1 |pages=76 |pmid= 26155935 |pmc= 4495609 |doi=10.1186/s13567-015-0199-7 |doi-access=free }}</ref> Humans are commonly infected after drinking [[Pasteurization|unpasteurized]] milk from affected animals or, less commonly, when coming into contact with infected tissues and liquids (afterbirth, etc.).<ref name="Scott 2011">{{cite book|editor1-last=Scott |editor1-first=PR |editor2-last=Penny |editor2-first=CD |editor3-last=Macrae |editor3-first=A |title= Cattle Medicine |url=https://archive.org/details/cattlemedicine00scot |url-access=limited |date=2011 |publisher= Manson Pub. |location=London |isbn= 978-1840766110 |page=[https://archive.org/details/cattlemedicine00scot/page/n34 34] |chapter= Brucellosis}}</ref>

The incubation period for the disease can range from 2 weeks to 1 year. Once symptoms begin to show, the host will be sick anywhere from 5 days to 5 months, depending on the severity of illness. A few of the symptoms of brucellosis include: fever, chills, headache, backache, and weight loss. As with any disease, there can be serious complications; [[endocarditis]] and liver abscess are a couple of complications for brucellosis.<ref>{{Cite web |url= http://microbewiki.kenyon.edu/ |title= microbewiki |website= microbewiki.kenyon.edu |language=en |access-date= 2017-10-25}}</ref> Although rare, ''B. abortus'' (and other ''Brucella'' spp.) can be transmitted between humans, usually via sexual transmission.

''B. abortus'' also affects [[bison]].<ref>{{cite book |last1=Lott |first1=Dale F. |title= American bison: a natural history |url=https://archive.org/details/americanbisonnat00lott |url-access=limited |date=2002 |publisher= University of California Press |location=Berkeley |isbn= 978-0520233386 |page=[https://archive.org/details/americanbisonnat00lott/page/n157 109]}}</ref>

== Species ==
''Brucella'' has twelve different kinds of species, one being ''Brucella abortus''.<ref name=":0">{{Cite journal|title=''Brucella Abortus'': Determination of survival times and evaluation of methods for detection in several matrices|journal = BMC Infectious Diseases|volume = 18|issue = 1|pages = 259|pmc = 5989407|year = 2018|last1 = Kaden|first1 = R.|last2 = Ferrari|first2 = S.|last3 = Jinnerot|first3 = T.|last4 = Lindberg|first4 = M.|last5 = Wahab|first5 = T.|last6 = Lavander|first6 = M.|pmid = 29871600|doi = 10.1186/s12879-018-3134-5 | doi-access=free }}</ref> Some of the other species are known as ''[[Brucella melitensis|B. melitensis]], [[Brucella canis|B. canis]], [[Brucella suis|B. suis]], [[Brucella ovis|B. ovis]], B. neotomae, [[Brucella ceti|B. ceti]],'' and ''[[Brucella pinnipedialis|B. pinnipediae]]''. Each species displays an affinity for specific animals or groups of animals.<ref>{{Cite web|url=https://www.cdc.gov/brucellosis/clinicians/brucella-species.html|title=Humans and Brucella Species|date=13 June 2019 }}</ref> Cattle and other livestock are the major host species for the bacteria ''B. abortus''.<ref name=":0" /> It is usually found to colonize in the liver and spleen.

There are many different ways ''B. abortus'' can spread from the different animals and even to humans. Human infections can lead to Bang's disease.<ref name=":0" /> When cattle have [[stillbirth]]s and are carrying this disease, other animals nearby can get infected if they ingest it or otherwise come into contact with fluids containing the bacteria. It could also be passed by their semen and urine.<ref name=":1">{{Cite web|url=http://www.cfsph.iastate.edu/Factsheets/pdfs/brucellosis_abortus.pdf|title=Brucellosis: ''Brucella Abortus''}}</ref> Ticks are another source of transmission for ''B. abortus''.<ref name=":1" />

== Survival ==
Temperature plays a huge role in the survival of ''B. abortus''.<ref name=":2">{{Cite journal|title=Infectious Diseases: ''Brucella Abortus''|journal=BMC Infectious Diseases|volume=18|issue=1|pages=259|doi=10.1186/s12879-018-3134-5|pmid=29871600|pmc=5989407|year=2018|last1=Kaden|first1=R.|last2=Ferrari|first2=S.|last3=Jinnerot|first3=T.|last4=Lindberg|first4=M.|last5=Wahab|first5=T.|last6=Lavander|first6=M. |doi-access=free }}</ref> The bacteria can survive for a longer period of time if they are at a cooler temperature. This is why it can transmit through liquids like milk and tap water.<ref name=":2" /> ''B. abortus'' can last a lot longer in animals if they are not watched closely and if the cattle are not treated for it. In humans, it can be caught after noticing signs and the correct tests to determine the type of bacteria.<ref name=":1" />

==References==
{{Reflist}}

{{Taxonbar|from=Q11353905}}
{{Authority control}}

[[Category:Bacteria described in 1901]]
[[Category:Hyphomicrobiales]]
[[Category:Pathogenic bacteria]]

Anaplasma phagocytophilum

2025-05-07T13:43:29Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{Short description|Species of bacterium}}
{{Italic title}}
{{Speciesbox
| image = Anaplasma phagocytophilum cultured in human promyelocytic cell line HL-60.jpg
| image_caption = Human [[HL60]] cells containing ''Anaplasma phagocytophilum'' (indicated by arrows) which are basophilic intracytoplasmic inclusions when stained with [[Wright-Giemsa stain]]
| taxon = Anaplasma phagocytophilum
| authority = (Foggie 1949) Dumler et al. 2001<ref name=LSPN>[https://lpsn.dsmz.de/genus/anaplasma Page Anaplasma on lpsn.dsmz.de]</ref>
| synonyms = ''Rickettsia phagocytophila ovis''<br/>''Rickettsia phagocytophila''<br/>''Cytoecetes phagocytophila''<br/>''Cytoecetes phagocytophila''
}}

'''''Anaplasma phagocytophilum''''' (formerly '''''Ehrlichia phagocytophilum''''')<ref>{{cite journal |vauthors =Dumler JS, Barbet AF, Bekker CP |title=Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila |journal=Int. J. Syst. Evol. Microbiol. |volume=51 |issue=Pt 6 |pages=2145–65 |year=2001 |pmid=11760958 |doi=10.1099/00207713-51-6-2145|display-authors=etal|doi-access=free }}</ref> is a [[Gram-negative]] bacterium that is unusual in its [[tropism]] to [[neutrophils]]. It causes [[anaplasmosis]] in sheep and cattle, also known as '''tick-borne fever''' and '''pasture fever''', and also causes the [[zoonotic]] disease [[human granulocytic anaplasmosis]].<ref name="WikiVet">[http://en.wikivet.net/Tick-Borne_Fever Tick-Borne Fever] reviewed and published by [[WikiVet]], accessed 12 October 2011.</ref>

''A. phagocytophilum'' is a Gram-negative, [[obligate]] bacterium of neutrophils. It causes human [[Granulocyte|granulocytic]] anaplasmosis, which is a tick-borne rickettsial disease. Because this bacterium invades neutrophils, it has a unique adaptation and pathogenetic mechanism.<ref name=Dumler05>{{cite journal |vauthors =Dumler JS, Choi KS, Garcia-Garcia JC |title=Human granulocytic anaplasmosis and ''Anaplasma phagocytophilum'' |journal=Emerging Infect. Dis. |volume=11 |issue=12 |pages=1828–34 |date=December 2005 |pmid=16485466 |pmc=3367650 |doi=10.3201/eid1112.050898 |display-authors=etal}}</ref>

==Biology==
''A. phagocytophilum'' is a small, obligate, intracellular bacterium with a Gram-negative cell wall. It is 0.2–1.0 μm and lacks a lipopolysaccharide biosynthetic machinery. The bacterium first resides in an early [[endosome]], where it acquires nutrients for binary fission and grows into small groups called morulae. This bacterium prefers to grow within myeloid or granulocytic cells.<ref name=Dumler05 />

===Hosts===
Hosts include [[goat|goats]], [[cattle]], [[horse|horses]] and [[dog|dogs]]. Cattle infections had been suspected but were only first confirmed by Nieder et al. 2012.<ref name="Brown-Barbet-2016">{{cite journal | last1=Brown | first1=Wendy C. | last2=Barbet | first2=Anthony F. | title=Persistent Infections and Immunity in Ruminants to Arthropod-Borne Bacteria in the Family Anaplasmataceae | journal=[[Annual Review of Animal Biosciences]] | publisher=[[Annual Reviews (publisher)|Annual Reviews]] | volume=4 | issue=1 | date=2016-02-15 | issn=2165-8102 | doi=10.1146/annurev-animal-022513-114206 | pages=177–197| pmid=26734888 }}</ref>

==Role in human disease==
''A. phagocytophilum'' causes human granulocytic [[anaplasmosis]] (HGA). This disease was first identified in 1990, although this pathogen was known to cause veterinary disease since 1932. Since 1990, incidence of HGA has increased, and it is now recognized in Europe. This disease was first identified due to a Wisconsin patient who died with a severe febrile illness two weeks after a tick bite. During the last stage of the infection, a group of small bacteria was seen within the neutrophils in the blood. Other symptoms include fever, headache, absence of skin rash, [[leucopenia]], [[thrombocytopenia]], and mild injury to the liver.<ref name=Dumler05 />

==Clinical signs in animals==
The disease is multisystemic, but the most severe changes are [[anaemia]] and [[leukopenia]]. This organism causes [[lameness]], which can be confused with symptoms of [[Lyme disease]], another tick-borne illness. It is a vector-borne [[zoonotic disease]] whose morula can be visualized within [[neutrophil]]s (a type of white blood cell) from the peripheral blood and synovial fluid. It can cause [[lethargy]], [[ataxia]], [[loss of appetite]], and weak or painful limbs.<ref name="WikiVet"/>

==Bacterial mechanism==
''A. phagocytophilum'' binds to fucosylated and sialylated scaffold proteins on neutrophil and granulocyte surfaces. A [[type IV secretion apparatus]] is known to help in the transfer of molecules between the bacterium and the host. The most studied ligand is PSGL-1 ([[P-selectin glycoprotein ligand-1|CD162]]). The bacterium adheres to PSGL-1 (CD162) through the 44-kDa major surface protein-2 (Msp2). After the bacterium enters the cell, the endosome stops maturation and does not accumulate markers of late endosomes or [[phagolysosome]]s. Because of this, the vacuole does not become acidified or fused to [[lysosome]]s. ''A. phagocytophilum'' then divides until [[cell lysis]] or when the bacteria leave to infect other cells.<ref name=Dumler05 />

This bacterium has the ability to affect neutrophils by altering their function. It can survive the first encounter with the host cell by detoxifying [[superoxide]] produced by [[NADPH oxidase#Neutrophilic type|neutrophil phagocyte oxidase]] assembly. It also disrupts normal neutrophil function, such as endothelial cell adhesion, transmigration, motility, degranulation, respiratory burst, and phagocytosis.<ref name=Dumler05 /> It causes an increase in the secretion of [[Interleukin 8|IL-8]], a chemoattractant that increases the phagocytosis of neutrophils. The purpose of this is to increase bacterial dissemination into the neutrophil.<ref>{{cite journal |vauthors =Thomas V, Fikrig E |title=''Anaplasma phagocytophilum'' specifically induces tyrosine phosphorylation of ROCK1 during infection |journal=Cell. Microbiol. |volume=9 |issue=7 |pages=1730–7 |date=July 2007 |pmid=17346310 |doi=10.1111/j.1462-5822.2007.00908.x |s2cid=20043230 }}</ref>

==Laboratory diagnosis==
These tests can be performed to determine an ''A. phagocytophilum'' infection:
#Indirect immunofluorescence assay is the principal test used to detect infection. The acute and convalescent phase serum samples can be evaluated to look for a four-fold change in antibody titer to ''A. phagocytophilum''.
#Intracellular Inclusions (morulae) are visualized in granulocytes on Wright- or [[Giemsa stain|Giemsa-]] stained blood smears.
#Polymerase chain reaction assays are used to detect ''A. phagocytophilum'' DNA.<ref name="health.state">{{cite web |title=Human Anaplasmosis Information for Health Professionals: Diagnostic tests |work=Diseases |publisher=Minnesota Department of Health |url=http://www.health.state.mn.us/divs/idepc/diseases/anaplasmosis/hcp.html#tests |access-date=2011-04-27 |archive-url=https://web.archive.org/web/20190213103116/http://www.health.state.mn.us/divs/idepc/diseases/anaplasmosis/hcp.html#tests |archive-date=2019-02-13 |url-status=dead }}</ref>

[[File:Doxycycline 100mg capsules.jpg|thumb|Doxycycline]]

==Antibiotic therapy==
Patients with HGA undergo [[doxycycline]] therapy, 100 mg twice daily until the patient's fever subsides for at least 3 days. This drug has been the most beneficial to those patients infected with the bacteria. Some other [[tetracycline]] drugs are also effective. In general, patients with symptoms of HGA and unexplained fever after a tick exposure should receive empiric doxycycline therapy while their diagnostic tests are pending, especially if they experience [[leukopenia]] and/or [[thrombocytopenia]].<ref name="health.state" />

In animals, antibiotics such as [[oxytetracycline]], sulphamethazine, [[sulphadimidine]], [[doxycycline]], and [[trimethoprim]]-[[Sulfonamide (medicine)|sulphonamides]] have been used.<ref name="WikiVet"/>

== References ==
{{Reflist}}

== External links ==
* [https://web.archive.org/web/20080623201116/http://cmr.jcvi.org/tigr-scripts/CMR/GenomePage.cgi?org=gaph ''Anaplasma'' phagocytophilum HZ Genome Page]
* {{MeshName|Anaplasma+phagocytophilum}}
*{{cite journal |vauthors =Zhang L, Liu Y, Ni D |title=Nosocomial transmission of human granulocytic anaplasmosis in China |journal=JAMA |volume=300 |issue=19 |pages=2263–70 |date=November 2008 |pmid=19017912 |doi=10.1001/jama.2008.626 |display-authors=etal|doi-access=free }}

{{Gram-negative bacterial diseases}}
{{Taxonbar|from=Q292189}}

[[Category:Rickettsiales]]
[[Category:Bacteria described in 1949]]
[[Category:Pathogenic bacteria]]

Borrelia hermsii

2025-05-07T13:41:44Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{Short description|Species of bacterium}}
{{Speciesbox
| taxon = Borrelia hermsii
| authority = (Davis, 1942) Steinhaus, 1946
| image = Borrelia hermsii Bacteria (13758011613).jpg
| image_caption = ''Borrelia hermsii'' (green) on red blood cells
}}

'''''Borrelia hermsii''''' is a [[Spiral bacteria#Spirochete|spirochete]] bacterium representing the endemic causative agent of [[relapsing fever|tick-borne relapsing fever]] in eastern regions of [[North America]] (more specifically, the eastern United States, and British Columbia region of Canada). It is spread by the soft-bodied tick ''[[Ornithodoros hermsi]]''. Human infections characteristically occur among campers and people temporarily lodging in wooden accommodations in proximity to rodents. Human disease is usually relatively mild with low fever.<ref>{{Cite web |title=Dictionnaire médical de l'Académie de Médecine |url=https://www.academie-medecine.fr/le-dictionnaire/index.php?q=Borrelia+hermsii |access-date=2024-02-15 |website=www.academie-medecine.fr}}</ref>

== Epidemiology ==
''B. hermsii'' is endemic to regions of the U.S. with high elevation (whereas [[Borrelia turicatae|''B. turicatae'']] is endemic to low-lying regions such as Texas and Florida).<ref>{{Cite web |title=Relapsing Fever - Infectious Diseases |url=https://www.msdmanuals.com/professional/infectious-diseases/spirochetes/relapsing-fever |access-date=2024-02-15 |website=MSD Manual Professional Edition |language=en}}</ref>

==References==
{{reflist}}

{{Gram-negative non-proteobacterial bacterial diseases}}

{{Taxonbar|from=Q4946575}}

[[Category:Borrelia|hermsii]]
[[Category:Pathogenic bacteria]]

{{spirochaetes-stub}}

Borrelia recurrentis

2025-05-07T13:41:23Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{Short description|Species of bacterium}}
{{Speciesbox
|image= Borrelia recurrentis CDC.png
|image_caption = Photomicrographic view of a culture specimen showing ''Borrelia recurrentis'' bacteria
|genus = Borrelia
|species = recurrentis
|authority = (Lebert, 1874) Bergey et al., 1925
}}

'''''Borrelia recurrentis''''' is a species of ''[[Borrelia]]'', a [[spirochaete]] [[bacterium]] associated with [[relapsing fever]].<ref name="pmid9336893">{{cite journal |vauthors=Cutler SJ, Moss J, Fukunaga M, Wright DJ, Fekade D, Warrell D |title=Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp |journal=International Journal of Systematic Bacteriology |volume=47 |issue=4 |pages=958–68 |date=October 1997 |pmid=9336893 |doi=10.1099/00207713-47-4-958 |doi-access=free }}</ref><ref name="pmid16790790">{{cite journal |vauthors=Meri T, Cutler SJ, Blom AM, Meri S, Jokiranta TS |title=Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H |journal=Infection and Immunity |volume=74 |issue=7 |pages=4157–63 |date=July 2006 |pmid=16790790 |pmc=1489703 |doi=10.1128/IAI.00007-06 }}</ref> ''B. recurrentis'' is usually transmitted from person to person by the [[human body louse]].<ref name="isbn0-13-144329-1">{{cite book |author1=Madigan, Michael T. |author2=Martinko, John M. |title=Brock biology of microorganisms |publisher=Pearson Prentice Hall |location=Upper Saddle River, NJ |year=2006 |pages=410 |isbn=0-13-144329-1 }}</ref> Since the 1800s, the body louse has been known as its only known vector.<ref name="ReferenceA">{{cite journal | last1 = Boutellis | first1 = A | last2 = Mediannikov | first2 = O | last3 = Bilcha | first3 = KD | last4 = Ali | first4 = J | last5 = Campelo | first5 = D | last6 = Barker | first6 = SC | display-authors = etal | year = 2013| title = Borrelia recurrentis in head lice, Ethiopia | journal = Emerg Infect Dis | volume = 19| issue = 5| pages = 796–798| doi = 10.3201/eid1905.121480 | pmid = 23648147 | pmc = 3647509 }}</ref>

''B. recurrentis'' DNA was found in 23% of head lice from patients with louse-borne relapsing fever in Ethiopia. Whether head lice can transmit these bacteria from one person to another remains to be determined.<ref name="ReferenceA"/>

It is notable for its ability to alter the proteins expressed on its surface, which causes the "relapsing" characteristic of relapsing fever.<ref name="isbn0-7817-8215-5">{{cite book |author1=Fisher, Bruce |author2=Harvey, Richard P. |author3=Strohl, William A. |author4=Champe, Pamela C. |title=Lippincott's Illustrated reviews, microbiology |url=https://archive.org/details/microbiologylipp00harv |url-access=limited |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2007 |pages=[https://archive.org/details/microbiologylipp00harv/page/n177 166] |isbn=978-0-7817-8215-9 }}</ref>

==References==
{{Reflist}}

{{Gram-negative non-proteobacterial bacterial diseases}}
{{Taxonbar|from=Q139991}}
{{Authority control}}

[[Category:Borrelia|recurrentis]]
[[Category:Pathogenic bacteria]]

{{spirochaetes-stub}}

Borrelia burgdorferi

2025-05-07T13:40:21Z

2601:86:4380:8FC0:A52A:13F6:3A04:946F:

{{Short description|Species of bacteria}}
{{for-multi|the disease|Lyme disease|the species complex|Lyme disease microbiology}}
{{Speciesbox
| image = Borrelia burgdorferi (CDC-PHIL -6631) lores.jpg
| image_caption = ''Borrelia burgdorferi''
| taxon = Borrelia burgdorferi
| authority = Johnson et al. 1984 emend. Baranton et al. 1992
}}

'''''Borrelia burgdorferi''''' is a [[bacterial]] [[species]] of the [[Spirochaete|spirochete]] class in the [[genus]] ''[[Borrelia]]'', and is one of the causative agents of [[Lyme disease]] in humans.<ref>{{cite book|url=https://www.caister.com/lyme|title=Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions, and Disease Pathogenesis|publisher=Caister Academic Press|year=2021|isbn=978-1-913652-61-6|veditors=Radolf JD, Samuels DS}}</ref><ref name=Kath2021>{{cite journal |last1=Wolcott |first1=Katherine A. |last2=Margos |first2=Gabriele |last3=Fingerle |first3=Volker |last4=Becker |first4=Noémie S. |title=Host association of Borrelia burgdorferi sensu lato: A review |journal=Ticks and Tick-borne Diseases |date=September 2021 |volume=12 |issue=5 |pages=101766 |doi=10.1016/j.ttbdis.2021.101766 |pmid=34161868 }}</ref> Along with a few similar genospecies, some of which also cause Lyme disease, it makes up the [[species complex]] of ''Borrelia burgdorferi'' [[sensu lato]]. The complex currently comprises 20 accepted and 3 proposed genospecies.<ref name=Kath2021/> ''B. burgdorferi'' [[sensu stricto]] exists in North America and Eurasia and until 2016 was the only known cause of Lyme disease in North America.<ref>{{Cite web|url=https://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html|title=New Lyme-disease-causing bacteria species discovered|last=CDC|date=2016-02-08|website=Centers for Disease Control and Prevention|language=en-us|access-date=2019-01-18}}</ref><ref name="Borrelia">{{cite journal|last1=Tilly|first1=Kit|last2=Rosa|first2=Patricia A.|last3=Stewart|first3=Philip E.|title=Biology of Infection with Borrelia burgdorferi|journal=Infectious Disease Clinics of North America|date=2008|volume=22|issue=2|pages=217–234|doi=10.1016/j.idc.2007.12.013|pmid=18452798|pmc=2440571}}</ref><ref name=Kath2021/> ''B. burgdorferi'' are often mistakenly described as Gram negative because of their two external membranes, but they lack [[lipopolysaccharide]] and possess many surface lipoproteins, unlike true [[Gram-negative]] bacteria.<ref>{{cite book |editor= Samuels DS |editor2=Radolf, JD | year=2010 |title=''Borrelia'': Molecular Biology, Host Interaction and Pathogenesis | publisher=Caister Academic Press | isbn= 978-1-904455-58-5 | chapter=Chapter 6, Structure, Function and Biogenesis of the ''Borrelia'' Cell Envelope}}</ref>

==Microbiology==
''Borrelia burgdorferi'' is named after the researcher [[Willy Burgdorfer]], who first isolated the bacterium in 1982.<ref name="science1982">{{cite journal |vauthors=Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP |title=Lyme disease-a tick-borne spirochetosis? |journal=Science |volume=216 |issue=4552 |pages=1317–9 |date=June 1982 |pmid=7043737 |doi=10.1126/science.7043737 |bibcode=1982Sci...216.1317B|url=https://escholarship.org/uc/item/9vj3t37b }}</ref>
{| class="wikitable"
! Test type
! Test
! Characteristics
|-
| rowspan="4" |Colony characters
|Size
|Small<ref name=":0">{{Cite journal |last1=Kurtti |first1=T. J. |last2=Munderloh |first2=U. G. |last3=Johnson |first3=R. C. |last4=Ahlstrand |first4=G. G. |date=November 1987 |title=Colony formation and morphology in Borrelia burgdorferi |journal=Journal of Clinical Microbiology |volume=25 |issue=11 |pages=2054–2058 |doi=10.1128/jcm.25.11.2054-2058.1987 |issn=0095-1137 |pmid=3693538|pmc=269410 }}</ref>
|-
|Type
|Round<ref name=":0" />
|-
|Color
|White<ref name=":0" />
|-
|Shape
|Raised<ref name=":0" />
|-
|Morphological characters
|Shape
|Spirochete<ref name=":2">{{Cite journal |last1=Shi |first1=Wenyuan |last2=Yang |first2=Zhaomin |last3=Geng |first3=Yongzhi |last4=Wolinsky |first4=Lawrence E. |last5=Lovett |first5=Michael A. |date=January 1998 |title=Chemotaxis in Borrelia burgdorferi |journal=Journal of Bacteriology |volume=180 |issue=2 |pages=231–235 |doi=10.1128/JB.180.2.231-235.1998 |issn=0021-9193 |pmid=9440510|pmc=106876 }}</ref>
|-
| rowspan="2" |Physiological characters
|Motility
| +<ref name=":2" />
|-
|Growth at 6.5% NaCl
| +<ref name=":2" />
|-
| rowspan="5" |Biochemical characters
|Gram staining
| -
|-
|Oxidase
| -<ref name=":5">{{Cite journal |last1=Troxell |first1=Bryan |last2=Xu |first2=Haijun |last3=Yang |first3=X. Frank |date=2012-06-01 |title=Borrelia burgdorferi, a Pathogen That Lacks Iron, Encodes Manganese-dependent Superoxide Dismutase Essential for Resistance to Streptonigrin |journal=The Journal of Biological Chemistry |volume=287 |issue=23 |pages=19284–19293 |doi=10.1074/jbc.M112.344903 |issn=0021-9258 |pmc=3365960 |pmid=22500025|doi-access=free }}</ref>
|-
|Catalase
| -<ref name=":5" />
|-
|Oxidative-Fermentative
|Fermentative<ref>{{Citation |last1=Corona |first1=Arianna |title=''Borrelia burgdorferi'': Carbon Metabolism and the Tick-Mammal Enzootic Cycle |date=2015-08-04 |url=http://dx.doi.org/10.1128/9781555818883.ch8 |work=Metabolism and Bacterial Pathogenesis |pages=167–184 |place=Washington, DC, USA |publisher=ASM Press |access-date=2022-04-21 |last2=Schwartz |first2=Ira|volume=3 |issue=3 |doi=10.1128/9781555818883.ch8 |pmid=26185064 |pmc=7942402 |isbn=9781683670926 }}</ref>
|-
|β-Galactosidase
| +<ref>{{Cite journal |last1=Wasiluk |first1=Anna |last2=Waszkiewicz |first2=Napoleon |last3=Szajda |first3=Sławomir Dariusz |last4=Wojewódzka-Żelezniakowicz |first4=Marzena |last5=Kępka |first5=Alina |last6=Minarowska |first6=Alina |last7=Zwierz |first7=Zbigniew Wojciech |last8=Pancewicz |first8=Sławomir |last9=Ładny |first9=Jerzy Robert |last10=Zwierz |first10=Krzysztof |date=2012-07-05 |title=Alpha fucosidase and beta galactosidase in serum of a Lyme disease patients as a possible marker of accelerated senescence - a preliminary study |journal=Folia Histochemica et Cytobiologica |volume=50 |issue=2 |pages=270–274 |doi=10.5603/fhc.2012.0036 |issn=1897-5631 |pmid=22763966|doi-access=free }}</ref>
|-
| rowspan="4" |Utilization of
|Glycerol
| +<ref>{{Cite journal |last1=Pappas |first1=Christopher J. |last2=Iyer |first2=Radha |last3=Petzke |first3=Mary M. |last4=Caimano |first4=Melissa J. |last5=Radolf |first5=Justin D. |last6=Schwartz |first6=Ira |date=2011-07-07 |title=Borrelia burgdorferi Requires Glycerol for Maximum Fitness During The Tick Phase of the Enzootic Cycle |journal=PLOS Pathogens |volume=7 |issue=7 |pages=e1002102 |doi=10.1371/journal.ppat.1002102 |issn=1553-7366 |pmc=3131272 |pmid=21750672 |doi-access=free }}</ref>
|-
|Galactose
| +<ref name=":6">{{Cite journal |last1=Hulínská |first1=D. |last2=Volf |first2=P. |last3=Grubhoffer |first3=L. |date=April 1992 |title=Characterization of Borrelia burgdorferi glycoconjugates and surface carbohydrates |url=https://pubmed.ncbi.nlm.nih.gov/1611204/ |journal=Zentralblatt für Bakteriologie |volume=276 |issue=4 |pages=473–480 |doi=10.1016/s0934-8840(11)80672-9 |issn=0934-8840 |pmid=1611204}}</ref>
|-
|D-Glucose
| +<ref name=":6" />
|-
|D-Mannose
| +<ref name=":6" />
|}
''Borrelia burgdorferi'' is a [[microaerophile]], requiring small amounts of oxygen in order to undergo [[glycolysis]] and survive. Like all other ''Borrelia'' sps., this bacterium is also gram-negative and a spirochete. Borrelia colonies are often smaller, rounded, and white with an elevated center.<ref name=":0" /> ''B. burgdorferi'' possesses [[flagella]] that allow it motility. It may be oxidase negative, but ''B. burgdorferi'' possesses a gene coding for [[superoxide dismutase]]. This protein inhibits the accumulation of [[reactive oxygen species]] (ROS).<ref name=":5" /> The bacterium appears able to utilize many different [[monosaccharide]]s for use in energy production.<ref name=":6" />

===Morphology===
''B. burgdorferi'' resembles other [[spirochete]]s in that it has an outer membrane and inner membrane with a thin layer of [[peptidoglycan]] in between. It is characterized as having a flexible cell well and has cells that are long and cylindrical with them being roughly 1 micron wide. However, the outer membrane lacks [[lipopolysaccharide]]. Its shape is a flat wave. It is about 0.3 μm wide and 5 to 20 μm in length.<ref name=Motaleb2015>{{cite journal |vauthors=Motaleb MA, Liu J, Wooten RM |title=Spirochetal motility and chemotaxis in the natural enzootic cycle and development of Lyme disease |journal=Current Opinion in Microbiology |volume=28 |pages=106–13 |year=2015 |pmid=26519910 |pmc=4688064 |doi=10.1016/j.mib.2015.09.006 }}</ref>

''B. burgdorferi'' is a [[microaerophile|microaerobic]], motile spirochete with seven to 11 bundled perisplasmic [[Flagellum|flagella]] set at each end that allow the bacterium to move in low- and high-viscosity media alike, which is related to its high virulence factor.<ref>{{cite journal|last1=Motaleb|first1=Mohammed|last2=Corum|first2=Linda|last3=Bono|first3=James|last4=Elias|first4=Abdallah|last5=Rosa|first5=Patricia|last6=Samuels|first6=D. Scott|last7=Charon|first7=Nyles|title=Borrelia burgdorferi periplasmic flagella have both skeletal and motility functions|pmc=27121|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=97|issue=20|pages=10899–10904|year=2000|doi=10.1073/pnas.200221797|pmid=10995478|bibcode=2000PNAS...9710899M|doi-access=free}}</ref>

===Metabolism===
''B. burgdorferi'' is a slow-growing microaerophilic spirochete with a doubling time of 24 to 48 hours.<ref name=Zuckert2007>{{cite book |doi=10.1002/9780471729259.mc12c01s4 |chapter=Laboratory Maintenance of ''Borrelia burgdorferi'' |title=Current Protocols in Microbiology |year=2007 |last1=Zückert |first1=Wolfram R. |volume=4 |pages=12C.1.1–12C.1.10 |pmid=18770608 |isbn=978-0-471-72925-9 }}</ref>

=== Transformation ===
Bacterial [[Transformation (genetics)|transformation]] has been utilized by researchers in order to isolate specific pathogenic genes among the ''Borrelia burgdorferi''. ''B. burgdorferi'' strains appear to be highly insufficient for use in bacterial transformation due to the large amount of DNA needed for transformation, the time it takes to produce reliable transformants, and the influence of [[restriction modification system]]s.<ref>{{Cite journal |last1=Brisson |first1=Dustin |last2=Dykhuizen |first2=Daniel E |date=2004-10-01 |title=ospC Diversity in Borrelia burgdorferi |url=http://dx.doi.org/10.1534/genetics.104.028738 |journal=Genetics |volume=168 |issue=2 |pages=713–722 |doi=10.1534/genetics.104.028738 |pmid=15514047 |pmc=1448846 |issn=1943-2631}}</ref><ref>{{Cite journal |last1=Hyde |first1=Jenny A. |last2=Weening |first2=Eric H. |last3=Skare |first3=Jon T. |date=February 2011 |title=Genetic Manipulation of Borrelia burgdorferi |journal=Current Protocols in Microbiology |volume=CHAPTER |pages=Unit–12C.4 |doi=10.1002/9780471729259.mc12c04s20 |issn=1934-8525 |pmc=3561735 |pmid=21400675}}</ref> In fact, infectivity of ''B. burgdorferi'' often requires the gene ''[[pncA]]'', which is present on a bacterial plasmid that contains the gene ''bbe02'' that is highly selected against during transformation. Since these genes are often paired together, infectivity is selected against in transformation, counteracting research to pinpoint particular genes that function in pathogenicity of ''Borrelia burgdorferi''.<ref>{{Cite journal |last1=Brisson |first1=Dustin |last2=Drecktrah |first2=Dan |last3=Eggers |first3=Christian H. |last4=Samuels |first4=D. Scott |date=2012 |title=Genetics of Borrelia burgdorferi |journal=Annual Review of Genetics |volume=46 |pages=10.1146/annurev–genet–011112-112140 |doi=10.1146/annurev-genet-011112-112140 |issn=0066-4197 |pmc=3856702 |pmid=22974303}}</ref> Despite this, some headway has been made in unraveling the mysteries of ''B. burgdorferi,'' such as the discovery of gene ''[[cyaB]]'' as essential for mammalian infection.<ref>{{Cite journal |last1=Ante |first1=Vanessa M. |last2=Farris |first2=Lauren C. |last3=Saputra |first3=Elizabeth P. |last4=Hall |first4=Allie J. |last5=O'Bier |first5=Nathaniel S. |last6=Oliva Chávez |first6=Adela S. |last7=Marconi |first7=Richard T. |last8=Lybecker |first8=Meghan C. |last9=Hyde |first9=Jenny A. |date=2021-05-25 |title=The Borrelia burgdorferi Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection |journal=Frontiers in Microbiology |volume=12 |pages=676192 |doi=10.3389/fmicb.2021.676192 |issn=1664-302X |pmc=8186283 |pmid=34113333|doi-access=free }}</ref>

==Life cycle==
''B. burgdorferi'' circulates between ''[[Ixodes]]'' ticks and a [[vertebrate]] host in an [[sylvatic cycle|enzootic cycle]].<ref name=Kath2021/> ''B. burgdorferi'' living in a tick is mainly acquired through blood meals from an infected, competent vertebrate host;<ref>{{cite journal |last1=Eisen |first1=Rebecca J. |last2=Eisen |first2=Lars |title=The Blacklegged Tick, Ixodes Scapularis: An Increasing Public Health Concern |journal=Trends in Parasitology |date=April 2018 |volume=34 |issue=4 |pages=295–6 |doi=10.1016/j.pt.2017.12.006 |pmid=29336985 |url= |pmc=5879012 }}</ref> rare cases of [[transovarial transmission]] have been reported, but may be attributable to ''[[Borrelia miyamotoi]]'', a related spirochete.<ref>{{cite journal |last1=Rollend |first1=Lindsay |last2=Fish |first2=Durland |last3=Childs |first3=James E. |title=Transovarial transmission of Borrelia spirochetes by Ixodes scapularis: A summary of the literature and recent observations |journal=Ticks and Tick-borne Diseases |date=February 2013 |volume=4 |issue=1–2 |pages=46–51 |doi=10.1016/j.ttbdis.2012.06.008 |pmid=23238242 }}</ref> Once a tick is infected, it will then transmit ''B. burgdorferi'' by feeding on another vertebrate to complete the cycle.<ref name="Brisson2012" /> Ticks can transmit ''B. burgdorferi'' to humans, but humans are dead-end hosts, unlikely to continue the life cycle of the spirochete.<ref name="Radolf2012">{{cite journal |vauthors=Radolf JD, Caimano MJ, Stevenson B, Hu LT |title=Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes |journal=Nature Reviews. Microbiology |volume=10 |issue=2 |pages=87–99 |year=2012 |pmid=22230951 |pmc=3313462 |doi=10.1038/nrmicro2714 }}</ref> Nymphs molt into adult ticks, which usually feed on larger mammals that are not able to support the survival of ''B. burgdorferi''.<ref name=Tilly2008>{{cite journal |vauthors=Tilly K, Rosa PA, Stewart PE |title=Biology of infection with Borrelia burgdorferi |journal=Infectious Disease Clinics of North America |volume=22 |issue=2 |pages=217–34, v |year=2008 |pmid=18452798 |pmc=2440571 |doi=10.1016/j.idc.2007.12.013 }}</ref>

==Disease==
{{Main|Lyme disease}}
''B. burgdorferi'' is the [[causative agent]] of [[Lyme disease]] and is why this bacteria is so important and being studied. It is most commonly transmitted from [[tick]]s to humans. Humans act as the tick's [[Host (biology)|host]] for this bacteria. Lyme disease is a [[Zoonosis|zoonotic]], [[Vector (epidemiology)|vector-borne disease]] transmitted by the ''[[Ixodes]]'' [[tick]] (also the vector for ''[[Babesia]]'' and ''[[Anaplasma]]''). The infected nymphal tick transmits ''B. burgdorferi'' via its saliva to the human during its blood meal.<ref name="Tilly2008"/>

Clinical presentation of Lyme disease is best known for the characteristic bull's-eye rash (also known as ''[[erythema chronicum migrans]]'') but can also include [[myocarditis]], [[cardiomyopathy]], [[arrhythmia]], [[arthritis]], [[arthralgia]], [[meningitis]], [[neuropathies]], and [[facial nerve palsy]]<ref name="Centers For Disease Control and Prevention">{{cite web | title = Signs and Symptoms, Lyme Disease |publisher= Centers For Disease Control| url = https://www.cdc.gov/lyme/signs_symptoms/ |date=March 4, 2015| access-date = 2015-07-16 }}</ref> depending on the stage of infection. [[File:Erythema migrans - erythematous rash in Lyme disease - PHIL 9875.jpg|right|thumb|Characteristic "bull's-eye" (erythema chronicum migrans) rash of stage 1 Lyme disease]]

''B. burgdorferi'' infections have been found in possible association with [[primary cutaneous diffuse large B-cell lymphoma]]s (PCDLBCLs),<ref name=Guidoboni_2006>{{cite journal |vauthors=Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R |title=Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives |journal=Clinical Lymphoma & Myeloma |volume=6 |issue=4 |pages=289–300 |date=January 2006 |pmid=16507206 |doi=10.3816/CLM.2006.n.003}}</ref><ref name="ChangParsonnet2010">{{cite journal|last1=Chang|first1=A. H.|last2=Parsonnet|first2=J.|author2-link=Julie Parsonnet|title=Role of Bacteria in Oncogenesis|journal=Clinical Microbiology Reviews|volume=23|issue=4|year=2010|pages=837–857|issn=0893-8512|doi=10.1128/CMR.00012-10|pmid=20930075|pmc=2952975}}</ref> where a review of the primary literature has, as of 2010, noted that most of the PCBCLs examined have been 'unresponsive' to antibiotics;<ref name="ChangParsonnet2010"/>{{rp|846}} hence, as in the case of ''[[Chlamydophila psittaci]]'' association with ocular adnexal [[mucosa-associated lymphoid tissue lymphoma]] (MALT lymphoma), the working conclusion was that "if ''B. burgdorferi'' is truly associated with PCBCL, then there is wide geographic variability and other factors are probably involved".<ref name="ChangParsonnet2010"/>{{rp|846}}

Progression of the disease follows three stages.

=== Stage 1 ===
Stage 1 is known as the Early Localized stage and occurs approximately 3 days - 1 month after inoculation. It affects the local area around the bite and is characterized by local swelling and / or a red "bull's-eye" rash (also known as ''[[erythema chronicum migrans]]'') seen as an erythematous circle encircling a defined center that expands outward. It can get as large as 15 cm in diameter.<ref name=burg2013>{{cite book|last1=Tortora|first1=Gerard J.|last2=Funke|first2=Berdell R.|last3=Case|first3=Christine L.|title=Microbiology: An Introduction|date=2013|publisher=Pearson Education, Inc.|location=United States of America|isbn=978-0-321-73360-3|pages=658–659}}</ref>{{rp|658}} Once the rash starts to subside the first symptoms can manifest as "flu-like" symptoms. At this stage, antibiotics are most efficacious to prevent further growth and symptoms of the disease before the major symptoms manifest.<ref name=burg2013 />{{rp|659}}

=== Stage 2 ===
Stage 2 is known as the Early Disseminated stage and occurs weeks - months after infection if left untreated. The bacteria spreads via the blood through the body to affect the organs. It often presents with general symptoms such as fever, chills, fatigue, and lymphadenopathy as well as the organ-specific symptoms. It can affect the [[heart]] causing [[myocarditis]], as well as [[arrhythmia]]s such as [[atrioventricular block]]s (which if significant enough may require the insertion of a pacemaker). It can affect the musculoskeletal system causing non-inflammatory transient [[arthritis]] and / or [[arthralgia]]s. It can affect the nervous system manifesting as facial paralysis ([[Bell's palsy]], classically bilateral), fatigue, and loss of memory.{{citation needed|date=September 2022}}

=== Stage 3 ===
Stage 3 is known as the Late Disseminated stage and occurs months - years after the initial infection. Effects of the 3rd stage include [[encephalitis]] or meningitis,<ref name=burg2013 /> as well as migratory arthropathies (most commonly of the knee).<ref name=burg2013 />

[[Anaplasmosis]] and [[babesiosis]] are also common tick-borne pathogens carried by the Ixodes tick that infect humans similarly to ''Borrelia burgdorferi''.<ref name=":1">{{Cite journal|title = Coinfections Acquired from Ixodes Ticks|journal = Clinical Microbiology Reviews|date = 2006-10-01|issn = 0893-8512|pmc = 1592693|pmid = 17041141|pages = 708–727|volume = 19|issue = 4|doi = 10.1128/CMR.00011-06|first1 = Stephen J.|last1 = Swanson|first2 = David|last2 = Neitzel|first3 = Kurt D.|last3 = Reed|first4 = Edward A.|last4 = Belongia}}</ref> Consequently, it is possible for an Ixodes tick to coinfect a host with either two or all other diseases. When a host is coinfected, the combined effects of the diseases act synergistically, often proving to cause worse symptoms than a single infection alone<ref name=":1" /> Coinfected humans tend to display a more severe manifestation of Lyme disease. In addition, they tend to acquire a wider range of secondary symptoms, such as influenza-like symptoms.<ref name=":1" /> More studies and research must be done to determine the synergistic effect of co-infection and its effect on the human body.

===Variation of severity===
So far, there are three factors that may contribute to the severity of the clinical manifestation of Lyme Disease. The presence of ribosomal spacers, [[plasmid]]s, and the outer surface protein C (OspC) are indicators of the severity of the infection.<ref name=Weis2011 /> Additionally, humans, themselves, vary in their response to the infection.<ref name=Weis2011 /> The variation in response leads to different clinical manifestations and different infections to different organs.{{citation needed|date=September 2022}}


==Molecular pathogenesis==

After the pathogen is transmitted, it will acclimate to the mammalian conditions. ''Borrelia burgdorferi'' will change its [[glycoprotein]]s and [[protease]]s on its plasma membrane to facilitate its dissemination throughout the blood.<ref name=Weis2011>{{Cite journal|url = https://www.ncbi.nlm.nih.gov/books/NBK57011/|title = Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes: Workshop Report.|last = Weis|first = Janet|date = 2011|journal = The National Academies|pages = 97–101}}</ref> While infecting, ''B. burgdorferi'' will express proteins that will interact with [[Endothelium|endothelial cells]], [[platelet]]s, [[chondrocyte]]s, and the [[extracellular matrix]].<ref name=Weis2011 /> This interaction inhibits proper function of the infected areas, leading to the pathological manifestations of Lyme disease. In response, the host will initiate an [[Inflammation|inflammatory response]] to attempt to remove the infection.<ref name=Weis2011 />

''Borrelia burgdorferi'' also expresses at least seven plasminogen binding proteins for interference of [[factor H]] at the activation level. This is part of a [[complement system]] evasion strategy that leads to downstream blocking of immune response.<ref>{{cite journal | author = Zipfel P., Hallström T., Riesbeck K. | year = 2013 | title = Human complement control and complement evasion by pathogenic microbes – Tipping the balance | url = http://lup.lub.lu.se/record/4027108| journal = Molecular Immunology | volume = 56 | issue = 3| pages = 152–160 | doi=10.1016/j.molimm.2013.05.222| pmid = 23810413 }}</ref>

In addition, ''Borrelia burgdorferi'' has a strategy to directly inhibit the classical pathway of complement system. A borrelial lipoprotein BBK32, expressed on the surface of ''Borrelia burgdorferi'', binds the initiating protease complex C1 of the classical pathway. More specifically, BBK32 interacts with C1r subunit of C1. C-terminal domain of the BBK32 protein mediates the binding. As a result, C1 is trapped in an inactive form.<ref>Garcia, B.L., Zhi, H., Wager, B., Höök, M. & Skare, J.T. 2016, "Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex", PLoS Pathogens, vol. 12, no. 1</ref>

==Genome==
''B. burgdorferi'' (B31 strain) was the third microbial [[genome]] ever [[DNA sequencing|sequenced]], following the sequencing of both ''[[Haemophilus influenzae]]'' and ''[[Mycoplasma genitalium]]'' in 1995. Its linear chromosome contains 910,725 [[base pair]]s and 853 [[gene]]s.<ref name=Fraser1997>{{cite journal |vauthors=Fraser CM, Casjens S, Huang WM |display-authors=etal |title=Genomic sequence of a Lyme disease spirochaete, B. burgdorferi |journal=Nature |volume=390 |issue=6660 |pages=580–6 |date=December 1997 |pmid=9403685 |doi=10.1038/37551|bibcode = 1997Natur.390..580F|s2cid=4388492 |doi-access=free }}</ref> The sequencing method used was [[whole genome shotgun]]. The sequencing project, published in ''Nature'' in 1997 and ''Molecular Microbiology'' in 2000, was conducted at [[The Institute for Genomic Research]].<ref name=Casjens2000>{{cite journal |vauthors=Casjens S, Palmer N, van Vugt R, Huang WM, Stevenson B, Rosa P, Lathigra R, Sutton G, Peterson J, Dodson RJ, Haft D, Hickey E, Gwinn M, White O, Fraser CM |title=A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete ''B. burgdorferi'' |journal=Molecular Microbiology |volume=35 |issue=3 |pages=490–516 |year=2000 |pmid=10672174 |doi= 10.1046/j.1365-2958.2000.01698.x|doi-access= }}</ref> ''B. burgdorferi''{{'s}} genome consists of one megabase chromosome and an unusual variety of circular and linear plasmids ranging in size from 9 to 62 kilobases.<ref name=Brisson2012>{{cite journal |vauthors=Brisson D, Drecktrah D, Eggers CH, Samuels DS |title=Genetics of ''B. burgdorferi'' |journal=Annual Review of Genetics |volume=46 |pages=515–36 |year=2012 |pmid=22974303 |pmc=3856702 |doi=10.1146/annurev-genet-011112-112140 }}</ref> The megabase chromosome, unlike many other eubacteria, has no relation to either the bacteria's virulence or to the host-parasite interaction.<ref name=Fraser1997/> Some of the plasmids are necessary for the ''B. burgdorferi'' life cycle but not for propagation of the bacteria in culture.<ref name=Brisson2012/>

The '''genomic variations''' of ''B. burgdorferi'' contribute to varying degrees of infection and dissemination.<ref name=":4">{{Cite journal|title = Evolution of the Borrelia burgdorferi outer surface protein OspC.|journal = Journal of Bacteriology|date = 1995-06-01|issn = 0021-9193|pmc = 176990|pmid = 7768799|pages = 3036–3044|volume = 177|issue = 11|first1 = M.|last1 = Theisen|first2 = M.|last2 = Borre|first3 = M. J.|last3 = Mathiesen|first4 = B.|last4 = Mikkelsen|first5 = A. M.|last5 = Lebech|first6 = K.|last6 = Hansen|doi = 10.1128/jb.177.11.3036-3044.1995}}</ref> Each genomic group has varying '''antigens''' on its membrane receptor, which are specific to the infection of the host. One such membrane receptor is the surface protein OspC.<ref name=":4"/> The OspC surface protein is shown to be a strong indicator of the identification of genomic classification and the degree of dissemination.<ref name=":4"/> Varying number of OspC loci are indications and determinants for the variations of ''B.'' ''burgdorferi''.<ref name=":4"/> The surface protein is also on the forefront of current vaccine research for Lyme disease via ''Borrelia''.<ref>{{Cite journal|title = Vaccination against Lyme disease: past, present, and future|journal = Frontiers in Cellular and Infection Microbiology|date = 2013-02-12|issn = 2235-2988|pmc = 3569838|pmid = 23407755|volume = 3|pages = 6|doi = 10.3389/fcimb.2013.00006|first1 = Monica E.|last1 = Embers|first2 = Sukanya|last2 = Narasimhan|doi-access = free}}</ref>

== Bacteriophage ==
Relatively few [[bacteriophage]]s are known to infect ''B. burgdorferi''. Several phage particles were isolated and some evidence suggested that they had an 8-kb [[DNA|dsDNA]] [[genome]]. Among the best-studied ''Borrelia'' phages is φBB-1, a phage with a polyhedral head and a contractile tail of 90 nm in length.<ref>{{Cite journal|last1=Eggers|first1=C. H.|last2=Casjens|first2=S.|last3=Hayes|first3=S. F.|last4=Garon|first4=C. F.|last5=Damman|first5=C. J.|last6=Oliver|first6=D. B.|last7=Samuels|first7=D. S.|date=October 2000|title=Bacteriophages of spirochetes|url=https://pubmed.ncbi.nlm.nih.gov/11075907|journal=Journal of Molecular Microbiology and Biotechnology|volume=2|issue=4|pages=365–373|issn=1464-1801|pmid=11075907}}</ref><ref>{{Cite book|url=https://www.worldcat.org/oclc/47901873|title=The spirochetes : molecular and cellular biology|date=2001|publisher=Horizon Scientific|others=Milton H. Saier, Jorge García-Lara|isbn=1-898486-27-1|location=Wymondham|oclc=47901873}}</ref> φBB-1 was the first bacteriophage that provided evidence of [[Transduction (genetics)|transduction]] for lateral gene transfer in ''Borrelia'' species that cause Lyme Disease.<ref>{{Cite journal |last1=Eggers |first1=Christian H. |last2=Kimmel |first2=Betsy J. |last3=Bono |first3=James L. |last4=Elias |first4=Abdallah F. |last5=Rosa |first5=Patricia |last6=Samuels |first6=D. Scott |date=2001-08-15 |title=Transduction by φBB-1, a Bacteriophage of Borrelia burgdorferi |journal=Journal of Bacteriology |language=en |volume=183 |issue=16 |pages=4771–4778 |doi=10.1128/JB.183.16.4771-4778.2001 |issn=0021-9193 |pmc=99531 |pmid=11466280}}</ref> Current research aims to use bacteriophages as way of identifying virulence factors in spirochetes that lead to Lyme Disease.{{citation needed|date=September 2022}}

== Immune Response ==
Mounting a successful immune response to Lyme disease can be complex considering the amount of cells involved. There are two different aspects to the immune system that allow for rapid and long-lasting responses. The innate immune system allows for a rapid, non-specific response to a pathogen. While the adaptive immunes system allows for a more long-lasting response that is more specific. The macrophage is part of the innate immunity as it attempts to locate, bind, and phagocytose the bacteria into an endosome. This allows for killing of the pathogen. Cytokine release during this also helps to attack the bacteria. T-cells are part of the adaptive immunity. They are more specific and can differentiate into different types that all serve different roles. The ultimate goal of the T-cells is to produce cytokines that will recruit other immune cells to the infection to help fight it. Borrelia burgdorferi has the ability to avoid detection from host immune systems, which makes it difficult to attack the infection right when it starts. The bacteria utilizes the outer surface proteins and it able to switch between them, which makes detection rather difficult [43]. This is just one example of how this bacteria can invade the immune system and not be detected. The body response to this includes integration between the innate and adaptive immunity which, like previously mentioned, includes many players.

==Evolution==
Genetically diverse ''B. burgdorferi'' strains, as defined by the sequence of ''ospC'', are maintained within the Northeastern United States. [[Balancing selection]] may act upon ''ospC'' or a nearby sequence to maintain the genetic variety of ''B. burgdorferi''.<ref name=Kurtenbach2006>{{cite journal |vauthors=Kurtenbach K, Hanincová K, Tsao JI, Margos G, Fish D, Ogden NH |title=Fundamental processes in the evolutionary ecology of Lyme borreliosis |journal=Nature Reviews. Microbiology |volume=4 |issue=9 |pages=660–9 |year=2006 |pmid=16894341 |doi=10.1038/nrmicro1475 |s2cid=10877654 |doi-access=free }}</ref> Balancing selection is the process by which multiple versions of a gene are kept within the gene pool at unexpectedly high frequencies. Two major models that control the selection balance of ''B.burgdorferi'' is [[Frequency-dependent selection|negative frequency-dependent selection]] and [[Polymorphism (biology)|multiple-niche polymorphism]].<ref name=":3">{{Cite book|title = Borrelia: Molecular Biology, Host Interaction and Pathogenesis|url = https://books.google.com/books?id=1iHDrzSIcI0C|publisher = Horizon Scientific Press|date = 2010-01-01|isbn = 9781904455585|first = D. Scott|last = Samuels}}</ref> These models may explain how ''B. burgdorferi'' have diversified, and how selection may have affected the distribution of the ''B. burgdorferi'' variants, or the variation of specific traits of the species, in certain environments.{{citation needed|date=September 2022}}

===Negative-frequency dependent selection===
In negative frequency-dependent selection, rare and uncommon variants will have a selective advantage over variants that are very common in an environment.<ref name=":3" /> For ''B. burgdorferi'', low-frequency variants will be advantageous because potential hosts will be less likely to mount an immunological response to the variant-specific OspC outer protein.<ref name=":3" />

===Multiple-niche polymorphism===
Ecological niches are all of the variables in an environment, such as the resources, competitors, and responses, that contribute to the organism's fitness. Multiple-niche polymorphism states that diversity is maintained within a population due to the varying amount of possible niches and environments.<ref name=":3" /> Therefore, the more various niches the more likelihood of polymophrism and diversity. For ''B. burgdorferi'', varying vertebrae niches, such as deer and mice, can affect the overall balancing selection for variants.<ref name=":3" />

==See also==
* [[Jorge Benach]]
* [[Allen Steere]]
* [[Ötzi]]

==References==
{{Reflist}}

==Further reading==
* <ref>{{Cite journal |last1=Kumar |first1=Devender |last2=Ristow |first2=Laura C. |last3=Shi |first3=Meiqing |last4=Mukherjee |first4=Priyanka |last5=Caine |first5=Jennifer A. |last6=Lee |first6=Woo-Yong |last7=Kubes |first7=Paul |last8=Coburn |first8=Jenifer |last9=Chaconas |first9=George |date=2015-12-18 |editor-last=Samuels |editor-first=D. Scott |title=Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein |journal=PLOS Pathogens |language=en |volume=11 |issue=12 |pages=e1005333 |doi=10.1371/journal.ppat.1005333 |doi-access=free |issn=1553-7374 |pmc=4686178 |pmid=26684456}}</ref>
* {{cite journal |last1=Velázquez |first1=Encarna |last2=Peix |first2=Álvaro |last3=Gómez-Alonso |first3=Alberto |title=Microorganismos y cáncer: evidencias científicas y nuevas hipótesis |trans-title=Microorganisms and cancer: scientific evidence and new hypotheses |language=es |journal=Cirugía Española |date=March 2011 |volume=89 |issue=3 |pages=136–144 |doi=10.1016/j.ciresp.2010.08.006 |pmid=21292247 }}
* {{cite journal |last1=Koči |first1=Juraj |last2=Bista |first2=Sandhya |last3=Chirania |first3=Payal |last4=Yang |first4=Xiuli |last5=Kitsou |first5=Chrysoula |last6=Rana |first6=Vipin Singh |last7=Yas |first7=Ozlem Buyuktanir |last8=Sonenshine |first8=Daniel E. |last9=Pal |first9=Utpal |title=Antibodies against EGF-like domains in Ixodes scapularis BM86 orthologs impact tick feeding and survival of Borrelia burgdorferi |journal=Scientific Reports |date=17 March 2021 |volume=11 |issue=1 |pages=6095 |doi=10.1038/s41598-021-85624-5 |pmid=33731754 |pmc=7971074 |bibcode=2021NatSR..11.6095K }}

==External links==
{{Wikispecies}}
{{Scholia|topic}}
* [https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138 NCBI Borrelia Taxonomy Browser]
* [https://web.archive.org/web/20090627232326/http://cmr.jcvi.org/tigr-scripts/CMR/GenomePage.cgi?database=gbb Borrelia burgdoferi B31 Genome Page]

{{Gram-negative non-proteobacterial bacterial diseases}}
{{Taxonbar|from=Q2723634}}
{{Authority control}}

[[Category:Bacteria described in 1992]]
[[Category:Borrelia|burgdorferi]]
[[Category:Lyme disease]]
[[Category:Suicide-inducing parasitism]]
[[Category:Pathogenic bacteria]]

[[de:Borrelien]]