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174 Biography and research experience Professor Francis Dziva is a member of the Royal College of Veteri- nary Surgeons UK with specialist training MSc and PhD in micro- biology. His research spanned nearly all key areas of veterinary bacteriology among them unravelling bacterial and host factors that influence the outcome of infection.Research on bacteria-host interactions contributed the majority of his research output in the UK where he was a principal investigator prior to joining The University of the West Indies. These studies focussed on food- producing ruminants and employed multidisciplinary approaches ranging from molecular tools cellular immunological and whole animal approaches. Mechanisms of Shiga toxin- producing ESCHERICHIA COLI STEC O157H7 persistence in cattle Whilst apparently healthy ruminants are important sources of food meat and milk they can carry one of the deadliest bacterium Shiga toxin-producing Escherichia coli O157H7 in their intestines without suffering or showing any symptoms. This organism can cause so-called attaching and effacing lesions in the intestine which is characterised by tightly attached bacteria sitting on a raised pedestal as shown above. Of greater significance is that this bacterium can multiply to several millions in the intestines of cattle and become intermittently shed in faeces increasing the chances of contaminating our food meat milk fruit and vegeta- bles water and the environment. Therefore direct or indirect contact with ruminant faeces is the leading antecedent to human infections. A serious concern is that only 100 bacterial cells are enough to cause acute disease in humans. Although cattle can harmlessly carry millions of this organism in the intestines the story is not the same when the bacterium transfers to humans.The disease in humans manifests as acute gastroenteritis haemor- rhagic colitis that may be complicated by life-threatening kidney disease haemolytic uremic syndrome HUS in those with weak immunity the youngelderly and the immunocompromised.HUS is characterised by acute kidney failure haemolytic anaemia and depleted blood clotting factors platelets. In rare cases severe neurological complications may occur. To understand how E. coli O157H7 persists in cattle Professor Dzivas work involved a combination of genetic tools to create 3000 random mutants mutant bank or library each containing a unique DNA sequence called a signature tag. The mutants were arrayed in micro-titre plates and fed in pools of 95 to cattle held in a high level of biosafety containment.Mutants defective in intesti- nal colonization were allowed to be shed in faeces within four days. At five days faeces were collected and bacterial mutants representative of those that were initially fed were collected in sufficient numbers. By comparing the composition of what was fed input and what came out in faeces output defective mutants were identified and the site of the signature tag within the genome was identified. This led to the first comprehensive portfolio of E.coli O157H7 genes required for persistence in cattle. Targeted mutations were constructed in individual genes to confirm their phenotypes in the target host by analysing their colonization patterns compared with the parent strain. It is clear that cattle are a key control point for E. coli O157H7 infections in humans. Intervention strategies that reduce pre-harvest carriage by cattle are also expected to lead to the lowering of the incidence of disease in humans. Subsequently recombinant vaccines based on identified genes with attenuating effect were tested for their ability to reduce carriage of this bacterium in cattle. These were not protective despite inducing strong antibody responses. However it was later shown by a Canadian group that it is the native rather than the recombinant proteins that lead to reduced carriage of E.coli O157H7 in cattlepaving the way to the first vaccine against this bacterium. Thus my studies were a fore- runner to the first commercial vaccine of E.coli O157H7. Work in this area has been extended to Trinidad by first determining the prevalence of this organism or related strains carrying Shiga toxin genes in cattle sheep and goats. Prof Dzivas graduate student has shown that Shiga toxin-producing E.coli are present in the dairy cattle herds as well as sheep and goats the strains are different from the classical E. coli O157H7 but are similar to those often seen in Australia. Ongoing work aims to determine the full repertoire of key virulence genes associated with disease in humans and their genetic relationship to other sequenced strains. Mechanisms of avian pathogenic ESCHERICHIA COLI APEC virulence in poultry and prospects for control Extending the same genetic approaches to a related organism avian pathogenic Escherichia coli APEC that causes a recalcitrant infection in poultry Professor Dziva has identified numerous genes that are now targets for developing live-attenuated vaccines of this key endemic disease. APEC causes a severe systemic disease in farmed poultry and is a disease of economic MEDICAL SCIENCES Professor in Veterinary Bacteriology Department of Basic Veterinary Sciences Tel 868 645 2640 ext. 4219 E-mail PROF. FRANCIS DZIVA