Page 1
Page 2
Page 3
Page 4
Page 5
Page 6
Page 7
Page 8
Page 9
Page 10
Page 11
Page 12
Page 13
Page 14
Page 15
Page 16
Page 17
Page 18
Page 19
Page 20
Page 21
Page 22
Page 23
Page 24
Page 25
Page 26
Page 27
Page 28
Page 29
Page 30
Page 31
Page 32
Page 33
Page 34
Page 35
Page 36
Page 37
Page 38
Page 39
Page 40
Page 41
Page 42
Page 43
Page 44
Page 45
Page 46
Page 47
Page 48
Page 49
Page 50
Page 51
Page 52
Page 53
Page 54
Page 55
Page 56
Page 57
Page 58
Page 59
Page 60
Page 61
Page 62
Page 63
Page 64
Page 65
Page 66
Page 67
Page 68
Page 69
Page 70
Page 71
Page 72
Page 73
Page 74
Page 75
Page 76
Page 77
Page 78
Page 79
Page 80
Page 81
Page 82
Page 83
Page 84
Page 85
Page 86
Page 87
Page 88
Page 89
Page 90
Page 91
Page 92
Page 93
Page 94
Page 95
Page 96
Page 97
Page 98
Page 99
Page 100
Page 101
Page 102
Page 103
Page 104
Page 105
Page 106
Page 107
Page 108
Page 109
Page 110
Page 111
Page 112
Page 113
Page 114
Page 115
Page 116
Page 117
Page 118
Page 119
Page 120
Page 121
Page 122
Page 123
Page 124
Page 125
Page 126
Page 127
Page 128
Page 129
Page 130
Page 131
Page 132
Page 133
Page 134
Page 135
Page 136
Page 137
Page 138
Page 139
Page 140
Page 141
Page 142
Page 143
Page 144
Page 145
Page 146
Page 147
Page 148
Page 149
Page 150
Page 151
Page 152
Page 153
Page 154
Page 155
Page 156
Page 157
Page 158
Page 159
Page 160
Page 161
Page 162
Page 163
Page 164
Page 165
Page 166
Page 167
Page 168
Page 169
Page 170
Page 171
Page 172
Page 173
Page 174
Page 175
Page 176
Page 177
Page 178
Page 179
Page 180
Page 181
Page 182
Page 183
Page 184
Page 185
Page 186
Page 187
Page 188
Page 189
Page 190
Page 191
Page 192
Page 193
Page 194
Page 195
Page 196
Page 197
Page 198
Page 199
Page 200
Page 201
Page 202
Page 203
Page 204
Page 205
Page 206
Page 207
Page 208
Page 209
Page 210
Page 211
Page 212
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 francis.dzivasta.uwi.edu PROF. FRANCIS DZIVA