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词条 Brachyspira
释义

  1. Phylogeny

  2. Evolutionary hypothesis

  3. Pathogenesis of human intestinal spirochetosis (HIS)

  4. Clinical manifestations in human medicine

  5. Antibiotic treatment and resistances in human medicine

  6. Antibiotic treatment and resistances in veterinary medicine

  7. Microbiologic identification

  8. Change in ecology

  9. References

{{Italic title}}{{Taxobox
| color = lightgrey
| name = Brachyspira
| regnum = Bacteria
| phylum = Spirochaetes
| classis = Spirochaetes
| ordo = Brachyspirales
| familia = Brachyspiraceae
| genus = Brachyspira Hovind-Hougen et al. 1983
| subdivision_ranks = Species
| subdivision =
  • Brachyspira aalborgi Hovind-Hougen et al. 1983 emend. Ochiai, Adachi & Mori 1998 non Foliella non Pfeiffer 1855
  • Brachyspira alvinipulli Stanton et al. 1998
  • Brachyspira canis ♠ (Duhamel et al. 1998) Oxberry & Hampson 2003
  • Brachyspira corvi ♠ Jansson et al. 2008
  • Brachyspira hampsonii ♠ Chander et al. 2012
  • Brachyspira hyodysenteriae (Harris et al. 1972) Ochiai et al. 1998
  • Brachyspira ibaraki ♠ (presumably an 16S-rDNA variant of B. aalborgi)[1] ♠ Tachibana et al. 2003
  • Brachyspira innocens (Kinyon and Harris 1979) Ochiai et al. 1998
  • Brachyspira intermedia (Stanton et al. 1997) Hampson and La 2006
  • Brachyspira murdochii (Stanton et al. 1997) Hampson and La 2006
  • Brachyspira pilosicoli (Trott et al. 1996) Ochiai et al. 1998
  • Brachyspira muridarum ♠ Backhans et al. 2010
  • Brachyspira muris ♠ Backhans et al. 2010
  • Brachyspira pulli ♠ Stephens and Hampson 2001
  • Brachyspira rattus ♠ Backhans et al. 2010
  • Brachyspira suanatina ♠ Rasback et al. 2007

| synonyms =
  • Serpula Stanton et al. 1991 non (Persson 1801) Gray 1821 non Linnaeus 1758
  • Serpulina Stanton 1992 non Zborzevski 1834

}}Brachyspira is a genus of bacteria classified within the phylum Spirochaetes.[2][3][4]

Brachyspira species include pathogens in pigs, birds, dogs, and humans.

B. pilosicoli colonizes millions of human worldwide leading to human intestinal spirochaetosis, a chronic intermittent watery diarrhea vastly underdiagnosed [5] because of the lack of simple diagnostic tool for clinicians. Multiplex qPCRs are promising diagnostic tools as Brachyspira do not grow on conventional media.[6]

B. pilosicoli also cause avian spirochetosis:[7] birds might be considered as the natural reservoir.

B. hyodysenteriae leads to diarrheal disease in growing pigs worldwide, causing the so-called swine dysentery, typhlocolitis or porcine intestinal spirochaetosis, which contributes to major "production losses" in agrobusiness.

Some species like B. innocens or B. intermedia seem to be less virulent.

Phylogeny

The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN)[8] and National Center for Biotechnology Information (NCBI),[9] and the phylogeny is based on 16S rRNA-based LTP release 123 by 'The All-Species Living Tree' Project.[10]

{{Clade | style=font-size:100%;line-height:80%
|1={{clade
|1=B. aalborgi Hovind-Hougen et al. 1983 (type sp.)
|12={{clade
|1=B. hyodysenteriae (Harris et al. 1972) Ochiai et al. 1998
|2={{clade
|1=B. innocens (Kinyon and Harris 1979) Ochiai et al. 1998
|2=B. murdochii (Stanton et al. 1997) Hampson and La 2006
|3={{clade
|1=B. intermedia (Stanton et al. 1997) Hampson and La 2006
|2={{clade
|1=B. alvinipulli Stanton et al. 1998
|2=B. pilosicoli (Trott et al. 1996) Ochiai et al. 1998
         }}       }}     }}   }}

}}

♠ Strains found at the National Center for Biotechnology Information (NCBI) but not listed in the List of Prokaryotic names with Standing in Nomenclature (LSPN).

Evolutionary hypothesis

It is interressant to consider that Brachyspira could be the missing link between independent gram-negatives and eventually internalized organisms like Mitochondria. One could imagine the following phylogenetic pathway: gram-negative free dwellers -> spirochetes attached to cell cytoskeleton and expressing porins creating cytoplasmic bridges and genome complementarity between parasite and mother cell -> rickettsia with full internalization --> permenent intracellular host = mitochondrium


Pathogenesis of human intestinal spirochetosis (HIS)

Brachyspira bacterias have evolved a parasitic lifestile through genomic reduction (~2.5 to 3.3 Mb) [11] compared to other gram negative bacteria (~5 Mb).

Humans infect themselves through dirty water ingestion, possibly by swimming in waters containing the bacteria or by direct oral exposure to contaminated feces (outdoor tribes, raw egg eaters, slum inhabitants with no sanitation, MSM).

Genome homologies between Borellia, Treponema and Brachyspira implies that Brachyspira is expected to:

  • import carbohydrates and short fatty acids (6->3 carbons) for its energetic needs from the colon lumen,
  • swim to (viscophily[12]) and through (viscotaxy) mucin layers thanks to its spiroid shape and flagellum (see film [13]),
  • attach to colonocytes apically and to each other laterally,
  • thereby creating a continuous and solidary layer of cells[14] which can withstand feces movement and replace natural villi in vivo: this is the pathognomonic brush-border [https://www.ncbi.nlm.nih.gov/pubmed/20200654] seen in histology on colonic biopsies.

Once attached apically to the enterocyte, hidden to the natural and acquired immunity by the mucous layer and occupying a niche that other bacterias cannot use, Brachyspira surely expresses at its apex porins [https://www.ncbi.nlm.nih.gov/pubmed/8955283] allowing it to import from the colonocyte's cytoplasm the amino acids and nucleic acids necessary to replicate.

It has also been demonstrated that Brachyspira creates an environment which is favorable to its locomotion by upregulating mucin expression:[15] it creates its own niche.

Clinical manifestations in human medicine

More and more publications tend to point out that Brachyspira colonization should NOT be considered a harmless commensal. Here is evidence of:

  • Chronic diarrhea [16]
  • Irritable bowel syndrome [17]
  • Appendicitis [18]
  • Ulcerative colitis [19]
  • Post translocation spirochetemia and cardiogenic shock [20]

Antibiotic treatment and resistances in human medicine

Treament with 10 days co-amoxicilline 1g bid + metronidazole 500 tid seems to have very good results on abdominal symptoms.[21] It is advised to administer Saccharomyces boulardii once a day during this course of antibiotherapy.[22]

Doxycyclin resistance has been documented and should be avoided.

Antibiotic treatment and resistances in veterinary medicine

Veterinary antibiotics used to treat pigs with dysentery due to Brachyspira species include the lincosamide lincomycin, the ionophore salinomycin, the quinoxaline carbadox, the pleuromodulins tiamulin and valnemulin, as well as the aminoglycoside gentamicin, an important antibiotic used in humans.

Brachyspira resistance to the above antibiotics has been increasingly reported. While no Clinical and Laboratory Standards Institute (CLSI) antimicrobial breakpoints for Brachyspira have been established, resistance to the pleuromutilins tiamulin and valnemulin is considered at MIC ≥ 2 µg/ml.[23] Resistance to pleuromutilins is important, because they are antibiotics of "last resort"; as of 2001, they were the only antibiotics with sufficient minimum inhibitory concentration (MIC) values left to treat swine dysentery in Sweden, per the National Veterinary Institute in Uppsala.[24]

Antibiotic resistance varies by geographic region and is not developing as rapidly in U.S. isolates as has been seen in isolates from other countries.[25]

Tiamulin resistance was first described in 1996 in Hungary,[26] and subsequently reported from other countries in Europe and Asia,.[27][28][29][30][31][32]

In Spain, 7.4% of Brachyspira isolates were reported to be venamulin resistant and 17.6% were tiamulin resistant in 2009.[33] In Sweden, 10-15% of B. pilosicoli isolates between 2002 and 2010 were resistant to tiamulin (MICs >4 μg/ml), and a gradual increase in tiamulin MICs was seen in B. hyodysenteriae between 1990 and 2003, which has since plateaued.[34]

Decreased susceptibility to lincomycin, but not to tiamulin was found among Polish isolates.[35]

In the USA, resistance of Brachyspira species collected 2008–2010 was common only against lincomycin (80% had MIC of 32 or 64), MIC's were moderatetly high against gentamicin, while resistance to valnemulin(4.7%) and tiamulin (3.2% of isolates) was yet uncommon, as reported in the only U.S. study to date, from Iowa.[25]

The use of pleuromutilins in U.S. food animals is not separately reported in the U.S. Food and Drug Administration's annual Animal Drug User Fee Act (ADUFA) report, "Antimicrobials Sold or Distributed for Use in Food-Producing Animals".[36] However, the amount of 190 t of lincosamides used is substantial per ADUFA; antibiotics used in the U.S. in food animals in 2011 was: Ionophores 4,123,259 kg, aminoglycosides 214,895 kg, and Lincosamides 190,101 kg.

Microbiologic identification

Brachyspira are capable of hemolysis, the degree of which has been used to characterize them, with B. hyodysenteriae showing strong beta hemolysis while B. pilosicoli, B. intermedia, B. murdochii, and B. innocens have been described as weakly hemolytic.[37] However, in a recent study from Iowa State University, all (10/10) B. intermedia isolates, 91% (9/11) of Brachyspira spp. isolates, and 20% (2/6) of B. pilosicoli isolates from farms in North Carolina (36), Iowa (23), Minnesota (9), Nebraska (3), Michigan (2), Illinois (2), Missouri (1), North Dakota (1), South Dakota (1), and Ohio (1), demonstrated strong beta-hemolysis.[25]

Recently quantitative PCR seems to be a more sensitive way to identify Brachyspira, which is globally a very fastidious bacteria to grow.

Change in ecology

In the U.S.A. Brachyspira-associated pig disease and isolation of Brachyspira species from swine with diarrheal disease largely disappeared from swine herds in the late 1990s and early 2000s, but returned in the mid-2000s for unknown reasons.

A 2011 study of isolates from Midwestern swine herds described major changes in Brachyspira spp frequency and hemolysis, i.e. pathogenicity: the majority of isolated Brachyspira species were previously considered minimally pathogenic or commensal, like Brachyspira murdochi (27%)or novel/unclassifiable Brachyspira species (25%), while only 40.5% of 79 isolates from diseased pigs could be confirmed as the classic pathogens B. hyodysenteriae or Brachyspira pilosicoli by PCR.[38]

Brachyspira species previously capable of weak hemolysis only, like B. intermedia and B. pilosicoli were found to produce strong hemolysis. They were also frequently identified from diseased swine which suggests they are emerging pathogens.

A compelling explanation for this change in epidemiology and ecology is selection by the increasing use of antibiotics in pigs (e.g. as growth promoters), since B. murdochii and unclassifiable Brachyspira spp. are less susceptible to antimicrobials than the previously established Brachyspira pathogens.

References

1. ^{{cite thesis |author = Westerman, L. J. |type = PhD thesis |date = 2013 |url = http://igitur-archive.library.uu.nl/dissertations/2013-1122-200600/UUindex.html |title = Human Intestinal Spirochaetosis }}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes }}
2. ^{{cite journal|title=Brachyspira pilosicoli-induced avian intestinal spirochaetosis|first1=Caroline I.|last1=Le Roy|first2=Luke J.|last2=Mappley|first3=Roberto M.|last3=La Ragione|first4=Martin J.|last4=Woodward|first5=Sandrine P.|last5=Claus|date=5 March 2019|publisher=|journal=Microbial Ecology in Health and Disease|volume=26|pages=28853|doi=10.3402/mehd.v26.28853|pmid=26679774|pmc=4683989}}
3. ^See the List of Prokaryotic names with Standing in Nomenclature. Data extracted from {{cite web |author = J.P. Euzéby |url = http://www.bacterio.cict.fr/classifphyla.html#Negativicutes |title = Spirochaetes |accessdate = 2011-11-17 |deadurl = yes |archiveurl = https://web.archive.org/web/20110613224152/http://www.bacterio.cict.fr/classifphyla.html#Negativicutes |archivedate = 2011-06-13 |df = }}
4. ^See the NCBI [https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=203691&lvl=6&lin webpage on Spirochaetes] Data extracted from {{cite web |author = Sayers| url=https://www.ncbi.nlm.nih.gov/Taxonomy/taxonomyhome.html/index.cgi |title=NCBI Taxonomy Browser |publisher=National Center for Biotechnology Information |accessdate=2011-06-05 |display-authors=etal}}
5. ^{{cite journal|title=The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans|first=David J.|last=Hampson|publisher=|journal=Clinical Microbiology Reviews|volume=31|issue=1|doi=10.1128/CMR.00087-17|pmid=29187397|pmc=5740978|year = 2017}}
6. ^{{cite journal|title=A novel multiplex qPCR targeting 23S rDNA for diagnosis of swine dysentery and porcine intestinal spirochaetosis|first1=Anna|last1=Borgström|first2=Simone|last2=Scherrer|first3=Constanze|last3=Kirchgässner|first4=Sarah|last4=Schmitt|first5=Daniel|last5=Frei|first6=Max M.|last6=Wittenbrink|date=7 February 2017|publisher=|journal=BMC Veterinary Research|volume=13|issue=1|pages=42|doi=10.1186/s12917-016-0939-6|pmid=28173799|pmc=5297149}}
7. ^{{cite journal|title=Brachyspira pilosicoli-induced avian intestinal spirochaetosis|first1=Caroline I.|last1=Le Roy|first2=Luke J.|last2=Mappley|first3=Roberto M.|last3=La Ragione|first4=Martin J.|last4=Woodward|first5=Sandrine P.|last5=Claus|date=5 March 2019|publisher=|journal=Microbial Ecology in Health and Disease|volume=26|pages=28853|doi=10.3402/mehd.v26.28853|pmid=26679774|pmc=4683989}}
8. ^{{cite web|url=http://www.bacterio.net/-classifphyla.html#Spirochaetes|title=Brachyspira|author=J.P. Euzéby|publisher=List of Prokaryotic names with Standing in Nomenclature (LPSN)|accessdate=2016-03-30}}
9. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=203691&lvl=6&lin|title=Brachyspira|author=Sayers|publisher=National Center for Biotechnology Information (NCBI) taxonomy database|accessdate=2016-03-30|display-authors=etal}}
10. ^'The All-Species Living Tree' Project.{{cite web|url=http://www.arb-silva.de/fileadmin/silva_databases/living_tree/LTP_release_123/LTPs123_SSU_tree.pdf|title=16S rRNA-based LTP release 123 (full tree)|publisher=Silva Comprehensive Ribosomal RNA Database|accessdate=2013-03-20}}
11. ^{{Cite journal |pmid = 28879525|year = 2018|last1 = Hampson|first1 = D. J.|title = Colonic Spirochetes: What Has Genomics Taught Us?|journal = Current Topics in Microbiology and Immunology|volume = 415|pages = 273–294|last2 = Wang|first2 = P.|doi = 10.1007/82_2017_48|isbn = 978-3-319-89637-3}}
12. ^{{cite journal|title=Attraction of Brachyspira pilosicoli to mucin|first1=Ram|last1=Naresh|first2=David J.|last2=Hampson|date=1 January 2010|publisher=|journal=Microbiology (Reading, England)|volume=156|issue=Pt 1|pages=191–197|doi=10.1099/mic.0.030262-0|pmid=19833772}}
13. ^[https://www.youtube.com/watch?v=yqkXk298RSI]
14. ^{{cite web|url=https://www.researchgate.net/figure/Transmission-electron-microscopic-view-of-sectioned-rectal-biopsy-specimen-showing-a_fig1_13798395|title=FIG. 1. Transmission electron microscopic view of sectioned rectal...|author=|date=|website=ResearchGate|access-date=5 March 2019}}
15. ^{{cite journal|title=Immunohistochemical study of mucins in human intestinal spirochetosis|first1=Sho|last1=Ogata|first2=Ken|last2=Shimizu|first3=Susumu|last3=Tominaga|first4=Kuniaki|last4=Nakanishi|publisher=|journal=Human Pathology|volume=62|pages=126–133|doi=10.1016/j.humpath.2017.01.013|pmid=28188751|year = 2017}}
16. ^{{cite journal|title=Human intestinal spirochetosis--a review|first1=Efstathia|last1=Tsinganou|first2=Jan-Olaf|last2=Gebbers|date=7 January 2010|publisher=|journal=German Medical Science: GMS e-Journal|volume=8|pages=Doc01|doi=10.3205/000090|pmid=20200654|pmc=2830567}}
17. ^{{cite journal|title=Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden|first1=Marjorie M.|last1=Walker|first2=Nicholas J.|last2=Talley|first3=Linn|last3=Inganäs|first4=Lars|last4=Engstrand|first5=Michael P.|last5=Jones|first6=Henry|last6=Nyhlin|first7=Lars|last7=Agréus|first8=Lars|last8=Kjellstrom|first9=Åke|last9=Öst|first10=Anna|last10=Andreasson|date=1 February 2015|publisher=|journal=Human Pathology|volume=46|issue=2|pages=277–283|doi=10.1016/j.humpath.2014.10.026|pmid=25540866}}
18. ^{{cite journal|title=Intestinal spirochaetosis mimicking acute appendicitis with review of the literature|first1=Jason|last1=Gan|first2=Catherine|last2=Bryant|first3=Dhili|last3=Arul|first4=Chetan|last4=Parmar|date=4 November 2017|publisher=|journal=BMJ Case Reports|volume=2017|pages = bcr-2017-221574|doi=10.1136/bcr-2017-221574|pmid=29103010}}
19. ^{{cite journal|title=Human intestinal spirochetosis mimicking ulcerative colitis|first1=Shin|last1=Nishii|first2=Masaaki|last2=Higashiyama|first3=Sho|last3=Ogata|first4=Shunsuke|last4=Komoto|first5=Suguru|last5=Ito|first6=Akinori|last6=Mizoguchi|first7=Hisato|last7=Terada|first8=Hirotaka|last8=Furuhashi|first9=Takeshi|last9=Takajo|first10=Kazuhiko|last10=Shirakabe|first11=Chikako|last11=Watanabe|first12=Kengo|last12=Tomita|first13=Shigeaki|last13=Nagao|first14=Soichiro|last14=Miura|first15=Ryota|last15=Hokari|date=1 April 2018|publisher=|journal=Clinical Journal of Gastroenterology|volume=11|issue=2|pages=145–149|doi=10.1007/s12328-017-0807-3|pmid=29204849}}
20. ^{{cite journal|title=Brachyspira pilosicoli bloodstream infections: case report and review of the literature|first1=Lilia|last1=Bait-Merabet|first2=Arnaud|last2=Thille|first3=Patrick|last3=Legrand|first4=Christian|last4=Brun-Buisson|first5=Vincent|last5=Cattoir|date=25 September 2008|publisher=|journal=Annals of Clinical Microbiology and Antimicrobials|volume=7|pages=19|doi=10.1186/1476-0711-7-19|pmid=18817558|pmc=2561035}}
21. ^{{cite journal|title=Intestinal Spirochetosis mimicking inflammatory bowel disease in children|first1=Rossana|last1=Helbling|first2=Maria-Chiara|last2=Osterheld|first3=Bernard|last3=Vaudaux|first4=Katia|last4=Jaton|first5=Andreas|last5=Nydegger|date=16 October 2012|publisher=|journal=BMC Pediatrics|volume=12|pages=163|doi=10.1186/1471-2431-12-163|pmid=23066991|pmc=3480841}}
22. ^{{cite journal|title=Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders|first1=Theodoros|last1=Kelesidis|first2=Charalabos|last2=Pothoulakis|date=1 March 2012|publisher=|journal=Therapeutic Advances in Gastroenterology|volume=5|issue=2|pages=111–125|doi=10.1177/1756283X11428502|pmid=22423260|pmc=3296087}}
23. ^Karlsson M,Fellström C, Johansson KE,Franklin A. Antimicrobial resistance in Brachyspira pilosicoli with special reference to point mutations in the 23S rRNA gene associated with macrolide and lincosamide resistance. Microb Drug Resist 2004. 10:204–208
24. ^Karlsson M, Gunnarsson A, Franklin A. Susceptibility to pleuromutilins in Brachyspira (Serpulina) hyodysenteriae. Anim Health Res Rev. 2001 Jun;2(1):59-65.
25. ^1 2 Clothier KA, Kinyon JM, Frana TS, Naberhaus N, Bower L, Strait EL, Schwartz K.Species characterization and minimum inhibitory concentration patterns of Brachyspira species isolates from swine with clinical disease.J Vet Diagn Invest. 2011 Nov;23(6):1140-5.
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28. ^Italy http://www.ivis.org/proceedings/ipvs/2006/TREATMENT/P_31-22.pdf?LA=1
29. ^Germany: Rohde J,Kessler M,Baums CG, Amtsberg G.Comparison of methods for antimicrobial susceptibility testing and MIC values for pleuromutilin drugs for Brachyspira hyodysenteriae isolated in Germany. Vet Microbiol 2004. 102:25–32.
30. ^Pringle M,Landén A,Franklin A. Tiamulin resistance in porcine Brachyspira pilosicoli isolates. Res Vet Sci 2006. 80:1–4.
31. ^Czech Republic: Lobová D, Smola J, Cizek A. Decreased susceptibility to tiamulin and valnemulin among Czech isolates of Brachyspira hyodysenteriae. J Med Microbiol 2004. 53:287–291.
32. ^Karlsson M. et al (2002). Proc. 17th IPVS Congr, p.189
33. ^Hidalgo A,Carvajal A, García-Feliz C,et al. Antimicrobial susceptibility testing of Spanish field isolates of Brachyspira hyodysenteriae. Res Vet Sci 2009. 87:7–12.
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35. ^Zmudzki J, Szczotka A, Nowak A, Strzelecka H, Grzesiak A, Pejsak Z.Antimicrobial susceptibility of Brachyspira hyodysenteriae isolated from 21 Polish farms.Pol J Vet Sci. 2012;15(2):259-65.
36. ^{{cite web|url=http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm338178.htm|title=Antimicrobials Sold or Distributed for Use in Food-Producing Animals|author=|date=|website=FDA.gov|access-date=5 March 2019}}
37. ^Komarek V,Maderner A,Spergser J,Weissenböck H. Infections with weakly haemolytic Brachyspira species in pigs with miscellaneous chronic diseases. Vet Microbiol 134: 311–317.
38. ^Clothier KA, Kinyon JM, Frana TS, Naberhaus N, Bower L, Strait EL, Schwartz K.Species characterization and minimum inhibitory concentration patterns of Brachyspira species isolates from swine with clinical disease.J Vet Diagn Invest. 2011 Nov;23(6):1140-5.
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2 : Spirochaetes|Gram-negative bacteria
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