Genetic studies in enteric bacteria

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The objective of work in my laboratory is to use the methods of genetics and genomics to reveal the basis for the astonishing degree of genetic variability which is found in bacterial populations. The over 2000 serovars of Salmonella vary dramatically, including S. enterica serovar Typhimurium which causes gastroenterites in many animals and humans, and S. enterica serovar Typhi which causes a much more serious enteric fever (Typhoid) only in humans, and thousands of other forms. I began studies in the 1960s by constructing a linkage map of the chromosome of S. Typhimurium with less than 200 genes mapped; in 2001 a collaborative effort with other labs sequenced about 4800 genes in the genome of the same bacterium. Sequence reveals that there are blocks of DNA, called Islands, in different serovars, which are present in some, but missing from others, and these produce different properties and virulence. Typhi has an Island which controls a virulence antigen; we have studied the loss of that island. In the coming grant period we have two major goals. (1) Comparative genomic analysis in enteric bacteria. We will be completing seven genomes which are being sequenced in our collaboration with Washington Univ. Genome Sequencing Center. We take part in gene annotation in these seven genomes, and overall comparisons of the genomes of all sequences to reveal phylogenetics, and to explain the basis for different phenotypes. (2) Study of the presence and role of prophages in bacterial genomes. Prophages are present in most genomes, e.g., S. Typhimurium strain LT2 has four. Whole genome sequencing reveals putative prophages based on bioinformatic studies, but we propose biological studies which will reveal if these are active prophages which can form free phage particles and transmit genes to other hosts.