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Review of the Food-borne Zoonoses Research ... - ARCHIVE: Defra

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Project code: OZ0607<br />

Project title: An investigation <strong>of</strong> <strong>the</strong> distinguishing features <strong>of</strong> C.<br />

jejuni strains that have host/disease associations.<br />

Start date (dd/mm/yy): 01/07/01<br />

End date (dd/mm/yy): 30/06/04<br />

£508,987<br />

Total cost:<br />

Affiliation: Veterinary Laboratories Agency (Weybridge)<br />

Sub-contractor(s):<br />

Abstract <strong>of</strong> research<br />

The attribution <strong>of</strong> poultry as <strong>the</strong> major source <strong>of</strong> human campylobacteriosis remains<br />

debatable. In order to inform risk assessment models, this project aimed to investigate<br />

<strong>the</strong> role <strong>of</strong> o<strong>the</strong>r livestock as potential sources and <strong>the</strong> possibility that all strains <strong>of</strong><br />

campylobacter were pathogenic for humans. A multi-pronged approach was <strong>the</strong>refore<br />

adopted to investigate <strong>the</strong> relationships between C.jejuni pathogenicity and host. Initial<br />

studies using higher disciminatory MLST-based approaches demonstrated that <strong>the</strong><br />

populations <strong>of</strong> C. jejuni from human cases and from colonised animals overlap<br />

significantly, indicating all veterinary campylobacters are potentially pathogenic to man.<br />

However, at least one host-associated cluster was evident in pigs. Additionally, genomic<br />

stability and instability were important factors in <strong>the</strong> ecology <strong>of</strong> this bacterial species.<br />

A second approach investigated <strong>the</strong> molecular pathogenesis <strong>of</strong> disease, in order to<br />

identify virulent and non-virulent organisms. In vitro assays indicated that <strong>the</strong>re were no<br />

obvious associations between genotype and putative campylobacter virulence properties,<br />

<strong>the</strong>refore, attempts were made to identify specific genetic markers <strong>of</strong> virulence. A<br />

transposon mutant library was produced and invasion-deficient mutants selected, which<br />

may provide future markers <strong>of</strong> invasiveness. Rapid molecular assays for screening CDT<br />

activity were developed and for <strong>the</strong> first time <strong>the</strong> immunogenicity <strong>of</strong> CDT was<br />

investigated using a novel neutralisation assay. Human anti-CDT antibodies were<br />

detectable in infected humans but no antibodies were detected in colonised chickens<br />

indicating a host-related specificity in response. Additionally significant progress was<br />

made on <strong>the</strong> identification <strong>of</strong> a fimbrial surface structure.<br />

Finally, a sentinel study was undertaken which demonstrated passage-associated<br />

changes in <strong>the</strong> genome sequence strain, NCTC11168, resulting in differences in chick<br />

colonisation, motility, morphology and invasiveness. Transcript analysis demonstrated<br />

changes in expression <strong>of</strong> a number <strong>of</strong> genes involved with <strong>the</strong> adaptation to microaerobic<br />

growth. This work is <strong>of</strong> huge significance to <strong>the</strong> research community by clarifying <strong>the</strong><br />

importance <strong>of</strong> strain origin in virulence and physiological studies.<br />

<strong>Review</strong> summary<br />

At <strong>the</strong> start <strong>of</strong> project OZ0607 it was beginning to be recognised that poultry is not <strong>the</strong><br />

only source for human campylobacter infection, and not all strains <strong>of</strong> campylobacter are<br />

pathogenic to humans. In order to more accurately attribute disease source and identify<br />

potential control measures, indicators <strong>of</strong> <strong>the</strong> relationships between strains, pathogenicity<br />

and host were required.<br />

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