24 research outputs found

    Genome variation and molecular epidemiology of Salmonella enterica serovar Typhimurium pathovariants

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    Salmonella enterica serovar Typhimurium is one of approximately 2,500 distinct serovars of the genus Salmonella but is exceptional in its wide distribution in the environment, livestock, and wild animals. S. Typhimurium causes a large proportion of nontyphoidal Salmonella (NTS) infections, accounting for a quarter of infections, second only to S. enterica serovar Enteritidis in incidence. S. Typhimurium was once considered the archetypal broad-host-range Salmonella serovar due to its wide distribution in livestock and wild animals, and much of what we know of the interaction of Salmonella with the host comes from research using a small number of laboratory strains of the serovar (LT2, SL1344, and ATCC 14028). But it has become clear that these strains do not reflect the genotypic or phenotypic diversity of S. Typhimurium. Here, we review the epidemiological record of S. Typhimurium and studies of the host-pathogen interactions of diverse strains of S. Typhimurium. We present the concept of distinct pathovariants of S. Typhimurium that exhibit diversity of host range, distribution in the environment, pathogenicity, and risk to food safety. We review recent evidence from whole-genome sequencing that has revealed the extent of genomic diversity of S. Typhimurium pathovariants, the genomic basis of differences in the level of risk to human and animal health, and the molecular epidemiology of prominent strains. An improved understanding of the impact of genome variation of bacterial pathogens on pathogen-host and pathogen-environment interactions has the potential to improve quantitative risk assessment and reveal how new pathogens evolve

    Bacteriophage Crosstalk: Coordination of Prophage Induction by Trans-Acting Antirepressors

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    Many species of bacteria harbor multiple prophages in their genomes. Prophages often carry genes that confer a selective advantage to the bacterium, typically during host colonization. Prophages can convert to infectious viruses through a process known as induction, which is relevant to the spread of bacterial virulence genes. The paradigm of prophage induction, as set by the phage Lambda model, sees the process initiated by the RecA-stimulated self-proteolysis of the phage repressor. Here we show that a large family of lambdoid prophages found in Salmonella genomes employs an alternative induction strategy. The repressors of these phages are not cleaved upon induction; rather, they are inactivated by the binding of small antirepressor proteins. Formation of the complex causes the repressor to dissociate from DNA. The antirepressor genes lie outside the immunity region and are under direct control of the LexA repressor, thus plugging prophage induction directly into the SOS response. GfoA and GfhA, the antirepressors of Salmonella prophages Gifsy-1 and Gifsy-3, each target both of these phages' repressors, GfoR and GfhR, even though the latter proteins recognize different operator sites and the two phages are heteroimmune. In contrast, the Gifsy-2 phage repressor, GtgR, is insensitive to GfoA and GfhA, but is inactivated by an antirepressor from the unrelated Fels-1 prophage (FsoA). This response is all the more surprising as FsoA is under the control of the Fels-1 repressor, not LexA, and plays no apparent role in Fels-1 induction, which occurs via a Lambda CI-like repressor cleavage mechanism. The ability of antirepressors to recognize non-cognate repressors allows coordination of induction of multiple prophages in polylysogenic strains. Identification of non-cleavable gfoR/gtgR homologues in a large variety of bacterial genomes (including most Escherichia coli genomes in the DNA database) suggests that antirepression-mediated induction is far more common than previously recognized
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