S. Typhi Mechanisms of Temperature- and Microbiota-Dependent Environmental Persistence

Denise Monack of Stanford University in the U.S. will use a genetic approach to identify the molecular mechanisms that enable the typhoid fever-causing bacterium S. Typhi to survive in aquatic environments and to rapidly adapt to transmission to humans. Annually, S. Typhi causes over 20 million infections and 200,000 deaths, mostly among populations that lack access to clean drinking water. Understanding how S. Typhi persists in water and then quickly adapts to its human host is critical for controlling transmission. Bacteria use various mechanisms to adapt to environmental changes, including so-called RNA thermometers (RNATs), which form secondary structures in mRNAs that can rapidly activate gene expression when temperatures change. They will use their established genetic screening approach to identify new RNATs in S. Typhi and validate their ability to promote bacterial persistence within aquatic microbial communities by generating mutants. They will also follow up on past work in which a bioinformatics approach identified new RNATs that may regulate the expression of the chitinase enzyme, which is used by the cholera-causing bacterium to bind to plankton and create a protective environmental niche. They will evaluate whether chitin is also important for S. Typhi persistence and transmission.