Research on improving food safety is an integral part of the GHFS Programme, a strategic programme funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major pathogen of animals and man in both industrial and developing nations. Part of what makes this pathogen so successful is its ability to invade our bodies and overcome our natural defences. Understanding how it does this could lead to new ways of preventing invasion and consequent infection.
Most Salmonella infections result in gastroenteritis when the bacteria invade the epithelial cells lining our gut. However, under certain conditions, Salmonella can subsequently cause a potentially lethal systemic typhoidal infection when they invade and grow within host cells of the monocyte/granulocyte lineage, including macrophages. Invasion of epithelial cells requires a cluster of genes localised in ‘Salmonella pathogenicity Island 1’ (SPI1), whereas replication and dissemination in macrophages requires a separate cluster of genes encoded within ‘Salmonella pathogenicity Island 2’ (SPI2). Some of the the genes within SPI1 and SPI2 encode a type III secretion system which injects effector proteins into the host cell resulting in either uptake of Salmonella (SPI1) or manipulation of the host cell environment to enable intracellular growth and subsequent dissemination of Salmonella (SPI2). Control of the expression of SPI1 and SPI2 is complex and occurs via a variety of factors, including proteins and alarmones, operating at transcriptional and post-transcriptional levels in response to the internal environmental stimuli of the host. Alarmones are small molecules in bacteria that are produced as a result of stress to the bacteria and act to alter gene expression within the bacteria. For example, we have previously shown that the alarmone ppGpp is required for the expression of nearly all of the genes within SPI1 and SPI2 as well as many other Salmonella-virulence related genes.
Until now, it has been unclear how the expression of SPI1 and SPI2 genes are synchronised to facilitate invasion by the bacteria and the subsequent development of a systemic infection. A new study, published in PLOS ONE, from a group within the GHFS Programme at the Institute of Food Research, has shown how two proteins (RpoS and DksA) and the alarmone ppGpp work together to modulate and thus coordinate the expression of SPI1 and SPI2 genes. This enables the ‘phased’ expression of SPI1 and SPI2 to facilitate Salmonella’s infection strategy.