Campylobacter

1. 1 ?????????? Campylobacter C. fetus veneralis C. fetus fetus C. jejuni / coli

2. 2 ??????: ???? ????? (????? ???) ?????? ?????????????? (???? ??????? ???' vibrio ??? ??? vibriosis ???? ?????? ?????? ??? ?????? ????? ?????? ?? ???? ?TCA ??? ???? ??????.

3. 3 ?????: ?????? ????? ??????? (????? ??????????? + ?????? (???? ??????? ?? ????) 5% ????, 10% CO2 ?%- ???? ?? ???? ????? ????? (48 ???? ?????)

4. 4 ???????? ?. ?'????: Heat labile + O antigens ?????? ?????? ??????? ?????????. ?? ?????? ?"? ?????? ???????.

5. 5 ???????? ?. ????: S-layer (surface array proteins)�SAP ???? ??????? ?? ?????? ?????? ??????? ??????? ???????????? ???? ???? ???????? ????. ?????? ????? 3C ??? ?????? (???? ??????????). ????? ???????? ??????? ?????. the S-layer confers resistance to complement mediated killing in non-immune serum by preventing the binding of complement factor C3b to the C. fetus cell surface. S-layer expressing C. fetus strains remain susceptible to complement independent killing, utilizing opsonic antibodies directed against the S-layer. ??????? ????? ???-????? ?? ??????? ??? ?????? ?? ???????????? ??? ?????? ???-?????? ????????? ???? ?? ?????? ?-O ?? ?-LPS ?? ??????? ???. Campylobacter Surface-Layers (S-Layers) and Immune Evasion Dr. Stuart A. Thompson Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia. Many pathogenic bacteria have evolved mechanisms for evading host immune systems. One evasion mechanism is manifest by the surface layer (S-layer), a paracrystalline protein structure composed of S-layer proteins (SLPs). The S-layer, possessed by 2 Campylobacter species (C. fetus and C. rectus), is external to the bacterial outer membrane and can have multiple functions in immune avoidance. C. fetus is a pathogen of ungulates and immunocompromised humans, in whom it causes disseminated bloodstream disease. In C. fetus, the S-layer is required for dissemination and is involved in 2 mechanisms of evasion. First, the S-layer confers resistance to complementmediated killing in non-immune serum by preventing the binding of complement factor C3b to the C. fetus cell surface. S-layer expressing C. fetus strains remain susceptible to complementindependent killing, utilizing opsonic antibodies directed against the S-layer. However, C. fetus has also evolved a mechanism for avoiding antibody-mediated killing by high-frequency antigenic variation of SLPs. Antigenic variation is accomplished by complex DNA inversion events involving a family of multiple SLPencoding genes and a single SLP promoter. Inversion events result in the expression of antigenically variant S-layers, which require distinct antibody responses for killing. C. rectus is implicated in the pathogenesis of periodontal disease and also possesses an S-layer that appears to be involved in evading the human system. Although studied less extensively than its C. fetus counterpart, the C. rectus S-layer appears to confer resistance to complement-mediated killing and to cause the down-regulation of proinflammatory cytokines. Ann Periodontol 2002;7:43-53. Campylobacter Surface-Layers (S-Layers) and Immune Evasion Dr. Stuart A. Thompson Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia. Many pathogenic bacteria have evolved mechanisms for evading host immune systems. One evasion mechanism is manifest by the surface layer (S-layer), a paracrystalline protein structure composed of S-layer proteins (SLPs). The S-layer, possessed by 2 Campylobacter species (C. fetus and C. rectus), is external to the bacterial outer membrane and can have multiple functions in immune avoidance. C. fetus is a pathogen of ungulates and immunocompromised humans, in whom it causes disseminated bloodstream disease. In C. fetus, the S-layer is required for dissemination and is involved in 2 mechanisms of evasion. First, the S-layer confers resistance to complementmediated killing in non-immune serum by preventing the binding of complement factor C3b to the C. fetus cell surface. S-layer expressing C. fetus strains remain susceptible to complementindependent killing, utilizing opsonic antibodies directed against the S-layer. However, C. fetus has also evolved a mechanism for avoiding antibody-mediated killing by high-frequency antigenic variation of SLPs. Antigenic variation is accomplished by complex DNA inversion events involving a family of multiple SLPencoding genes and a single SLP promoter. Inversion events result in the expression of antigenically variant S-layers, which require distinct antibody responses for killing. C. rectus is implicated in the pathogenesis of periodontal disease and also possesses an S-layer that appears to be involved in evading the human system. Although studied less extensively than its C. fetus counterpart, the C. rectus S-layer appears to confer resistance to complement-mediated killing and to cause the down-regulation of proinflammatory cytokines. Ann Periodontol 2002;7:43-53.

6. 6 ????? ??????: Motility and chemotaxis Chemoattraction towards bile and mucin allows colonization of the intestine and gall bladder adherence to epithelial cells Adherence with proteins, flagella and lipopolysaccharide. Campylobacter are adherent to cell membrane and are internalized into cytoplasmic vacuoles. flagellin and adhesion both are required for irreversible binding of bacteria to cells

7. 7 ????? ??????: Intracellular : C. fetus is capable of adhering, entering, and surviving within the nonphagocytic epithelial cells Proteins and enzymes cytolethal distending toxin (CDT) causes cellular distention and eventually death of the cell lines hemolysin. Catalase is required for Campylobacter hydrogen peroxide resistance as well as persistence in macrophages

8. 8 Cell Wall typical of gram-negative cells. three layers, an outer lipoprotein layer, a middle lipopolysaccharide layer inner mucopeptide layer. The LPS consisted of three distinct regions lipid A anchored in the outer membrane and is the endotoxic part of the LPS molecule. the core, which is attached to the lipid the O antigen attached to the outer core. The LPS molecules of Campylobacter are involved in adherence and play a role in antigenic variations, as Campylobacter has the ability to shift the LPS antigenic composition. Surprisingly N-acetyl neuraminic acid (sialic acid) is present in the core oligosaccharide, not frequently found in prokaryotes. These sialic acid residues appeared like gangliosides in structure, when attached to �D galactosidase. This molecular mimicry is involved in the neuropathological autoimmune diseases like Guillains Barre' Syndrome and Reiter syndrome.

9. 9 ????? ???? C. f. veneralis ???? ???? ????????? ?? ?????? ????? ???' ???? ????? ?????? (???? ???? ?????, ????? ????, ???? ?????????) . C.fetus fetus ???? ???? ???? ??? ??' ?????? ????? ?????? ?????? ????????, ???? ???? ????? ?????. ????? ?????? :commensals ?? ??' ?????? ?? ????, ???, ?????, ????? ????? ???? ?????.

10. 10 Survival in the Environment Survival of C. jejuni outside the gut is poor, and replication does not occur readily. C. jejuni grows best at 37�C to 42�C, the approximate body temperature of the chicken (41�C to 42�C). C. jejuni grows best in a low oxygen or microaerophilic environment, such as an atmosphere of 5% O2, 10% CO2, and 85% N2. The organism is sensitive to freezing, drying, acidic conditions (pH < 5.0), and salinity.

11. 11 ???????? C. jejuni / C.coli ????? ???????? (invasive ) ??? ????? ??????? ?? ???? ??? ?????? ?? ??' ??????. ????? (chemotaxis ) ?????? (mucin ) ???? ?????? ?????? ?? ???, ?????? ????? ????? ????. ????? ?????? ????? ????????? (?????). ????? ??? ????? ??? ???? ??? ?????? ??????? ????? ??????? ????? ???? ( ??? ??????, ??? ???? ????). produces an adhesin, a cytotoxin and a heat labile toxin (LPS) similar to E. coli.

12. 12 ????, ???, ????? : C. jejuni ???? ???' ?????? ??? ?????? ???????. ????? ????????. ???? ??? ??????.

13. 13 ?????? ??? ??? ?????? ???? ????? ????, ???? ?? ?? ??? ??.

14. 14 ????? ??????: ????, ????? ????, ?????? ???, ?????, ??? ???, ??? ???, ??? ?? ??????, ???, ????? ???????, ????? ????. ????? ?????? ?"? ?????? ??? ?? ????? ???"? ?? ??"? ?? ????.

15. 15

16. 16 Disease Prevalence In the United States, an estimated 2.1 to 2.4 million cases of human campylobacteriosis (illnesses ranging from loose stools to dysentery) occur each year. Commonly reported symptoms of patients with laboratory-confirmed infections (a small subset of all cases) include diarrhea, fever, and abdominal cramping. In one study, approximately half of the patients with laboratory-confirmed campylobacteriosis reported a history of bloody diarrhea. Less frequently, C. jejuni infections produce bacteremia, septic arthritis, and other extraintestinal symptoms. Centers for Disease Control and Prevention/U.S. Department of Agriculture/Food and Drug Administration Collaborating Sites Foodborne Disease Active Surveillance Network, 1996

17. 17

18. 18 Telegraph UK More than 160 mountain bikers made sick by sheep droppings 02 Dec 2008  � Public health inspectors were called in after the cyclists fell ill with food poisoning after an event in the Welsh countryside . The cyclists tested positive for the bacterium campylobacter � usually caused by uncooked meat and poultry. But following an investigation by health experts, the muddy mountain cycle course was found to be heavily contaminated with sheep droppings. The cyclists are believed to have been affected by eating meals and snacks during the event � without washing their hands first. "At that point we launched an internet based questionnaire to investigate the outbreak." More than 660 mountain bikers from all over Britain took part in the Builth Wells Mountain Biking Marathon in Powys in July this year. A total of 355 responses were received with 161 cyclists reporting symptoms such as diarrhoea and vomiting. The report, by the NPHSW, concluded the outbreak was caused by campylobacter spread to the cyclists by mud which was contaminated with sheep faeces. Heavy overnight rain is likely to have contributed to the outbreak by increasing the amount of liquid mud on the course. The report recommended cyclists to eat out of protective wrappers at future events.

19. 19 Sequelae to Infection Guillain-Barr� syndrome (GBS), a demyelating disorder resulting in acute neuromuscular paralysis, is a serious sequela of Campylobacter infection. An estimated one case of GBS occurs for every 1,000 cases of campylobacteriosis. Up to 40% of patients with the syndrome have evidence of recent Campylobacter infection . Approximately 20% of patients with GBS are left with some disability, and approximately 5% die despite advances in respiratory care.

20. 20 Guillain-Barre syndrome acute inflammatory demyelinating polyneuropathy (AIDP)

21. 21 GBS Pathogenesis precise mechanism of GBS is unclear. certainly has an immunological basis; most likely an autoimmunity triggered by an exogenous antigen. It has been linked epidemiologically to Campylobacter jejuni as well as other infectious agents. The preceding infection creates an immunological response to proteins epitopically similar to myelin.

22. 22 Sequelae to Infection Reiter syndrome Campylobacteriosis is also associated with Reiter syndrome, a reactive arthropathy. In approximately 1% of patients with campylobacteriosis, the sterile postinfection process occurs 7 to 10 days after onset of diarrhea. Multiple joints can be affected, particularly the knee joint. Pain and incapacitation can last for months or become chronic. Both GBS and Reiter syndrome are thought to be autoimmune responses stimulated by infection. The pathogenesis of GBS and Reiter syndrome is not completely understood.

23. 23 A survey of Campylobacter in animals.Manser PA, Dalziel RW.,Hyg (Lond). 1985 Aug;95(1):15-21 A survey of Campylobacter species in the faeces or rectal contents of domestic animals was carried out using direct and enrichment culture methods. Campylobacters were isolated from 259 (31%) of 846 faecal specimens. The highest isolation rate was found in pigs (66%); cattle (24%) and sheep (22%). In pigs all the isolates were C. coli, in sheep and cattle about 75% were C. jejuni. Only five isolations of C. fetus subsp. fetus were made, all from cattle. More pigs with diarrhoea had C. coli in their faeces than healthy pigs (77% vs 47%), but such a clear difference in isolation rate between sick and healthy animals was not seen in cattle or sheep. The results show that cattle, sheep and pigs constitute a large potential source of campylobacter infection for man.

24. 24 ????? ?????? ????? ???? ?????? ?????? ???? ?1.6% ?? 28% ?????? ??? ?????? ???????. ??????? ?? ?????? ??????? ???? ??????: ????? ???? ?? ???, ??? ????? ?? ????? ???? ?????? +/- ??? ???? ??"? 3-7 ???? ?? ???? ????? ???????? ???? ??????

25. 25

26. 26 Antimicrobial Resistance The increasing rate of human infections caused by antimicrobial-resistant strains of C. jejuni makes clinical management of cases of campylobacter more difficult. Antimicrobial resistance can prolong illness and compromise treatment of patients with bacteremia. The rate of antimicrobial-resistant enteric infections is highest in the developing world, where the use of antimicrobial drugs in humans and animals is relatively unrestricted.

27. 27 Antimicrobial Resistance Experimental evidence demonstrates that fluoroquinolone-susceptible C. jejuni readily become drug-resistant in chickens when these drugs are administered. After flouroquinolone use in poultry was approved in Europe, resistant C. jejuni strains emerged rapidly in humans during the early 1990s. Similarly, within 2 years of the 1995 approval of fluoroquinolone use for poultry in the United States, the number of domestically acquired human cases of ciprofloxacin-resistant campylobacteriosis doubled in Minnesota.

28. 28 Campylobacter fetus subsp veneralis ??? ????

29. 29 C. fetus veneralis ????? ???' ???? ??? ????? ???? ??? ???? ????? ?? ??????????? ??????? ??????????. ???? ??????? ???????????, ???? ?????? ???? ?????? ???? ???? ???????? cranial vagina, cervix, uterus and oviducts ? subacute endometritis with periglandular lymphocytic infiltration

30. 30 C. fetus veneralis ????? ?? IgG ???? ?- IgA ????? ??????? ????? ????? ?????. ( ??? ?? ???) ??? ????? ??? ?? ??' ?????? ????????. ????? ????? ?????? ?????? ?????? ???????????? ????? ???.

31. 31 ?????? ?????? ???? ?? - ??????: ???? ?? ????? ???? ??????? ???? ?????? - ????? ????? ??? ????? (??"? ???? ?10% ) ????? ??? ????? ???? ????.

32. 32 C. f. fetus ????? ???- ????? ??"? ???? ?????? ?????? ???? ????? ? ??????? ???? ???? ????? ? ???????? ?? ??? ? ???? ????? ???? ? ?????? ? ?????

33. 33 Campylobacter fetus subsp veneralis Few cases documented in man Debilitating factors (pregnancy, alcoholism, neoplasia, cardiac dis. Campylobacter fetus subsp fetus Septicemia 17% - 43% die Abortion, premature birth, full term birth which up to 50% may die of meningoencephalitis Campylobacter fetus in man

34. 34 ?????? ?????? ????? ?????? + ?????. ????? ??? ?????? ?"? ?????? ?????????, ?????? ?????? ???????? ?? ???????, ?????? ? 25 ?? 42 ?????. ??? ???. ????????????????? ???? ??????? - ?????- ?? ???? PCR

35. 35 ????? ?????? ?. ??????: ????? ???????? + ????? ?????. ??????????? ???? ???? ????? ?? ??????. ?????: ???'? ?????????????? ?????- ???? + ???'????

36. 36 ?. ???? ????: ???? � ????? ?????: ??????????????, ??????? ????? � ????? ???? ??? ????? ????? ?????? ????????

37. 37 ?. ?'????: ??"? ??? ???? ??????. ????? ??????? ?????? � ??????????? ??????? ????? ???? ?????? ???? ???. ???? ??? ???? ????? ????? ?????? ??? ????.

38. 38 Control of Campylobacter Infection On the Farm Control of Campylobacter contamination on the farm may reduce contamination of carcasses, poultry, and red meat products at the retail level. Epidemiologic studies indicate that strict hygiene reduces intestinal carriage in food-producing animals. In field studies, poultry flocks that drank chlorinated water had lower intestinal colonization rates than poultry that drank unchlorinated water. Experimentally, treatment of chicks with commensal bacteria and immunization of older birds reduced C. jejuni colonization. Because intestinal colonization with campylobacters readily occurs in poultry flocks, even strict measures may not eliminate intestinal carriage by food-producing animals.

39. 39 Important Tip!  Protect yourself against getting Campylobacter from animals. Simply wash your hands with running water and soap after any contact with animals and animal feces (stool).