Translational Reprogramming in Salmonella typhimurium Modifies Environmental pH to Sustain Higher Growth Rates before Entry into Stationary Phase

Abstract

Bacterial batch cultures in rich media are punctuated by differing substrate utilization patterns with corresponding changes in pH associated with the excreted metabolites. Salmonella typhimurium is an intracellular pathogen that is capable of replicating in highly acidic conditions such as macrophages. However, the biological mechanism which allows S.typhimurium to replicate in such hostile environments is still unclear. S.typhimurium grown in anaerobic conditions in LB displays an intriguing pH profile and a diauxic growth pattern, where the maximum growth rate corresponds to acidification of the surrounding medium, followed by a period of alkalization and a secondary growth burst corresponding to another cycle of acidification. We performed a high-throughput growth screen of a library of S.typhimurium non-essential gene deletions in anaerobic conditions and identified genes that are involved in the different phases of growth of S. typhimurium. We found that S.typhimurium follows distinct substrate utilization patterns in each phase of growth and that mutants that are unable to perform alkalization of the growth medium lack the observed secondary growth burst. We discovered that deletions of two genes epmA and epmB, that help alleviate translational pausing at poly-proline stretches, are unable to perform alkalization of the growth medium and hence have lower secondary growth rates. We postulate that S.typhimurium's growth advantage in low pH environments is conferred by global translational reprogramming allowing for easy switching between different metabolic states.