NtrC expression at lag-phase improves competitive fitness under low and fluctuating nutrient condition

Abstract

The enteric pathogens cycle between nutrient rich host and nutrient poor external environment. These pathogens compete for nutrients in the host as well as in external environment and also often experience starvation. In this context, we have studied the role of a global nitrogen regulator (NtrC) of Salmonella Typhimurium. The ntrC mutation caused extended lag phase and slow growth in minimal media. In lag phase the wild-type cells showed [~]60 fold more expression of ntrC as compared to log phase cells. The role of ntrC gene is often studied with respect to nitrogen scavenging in a low nitrogen growing condition. However, our observation indicates that, even in the adequate supply of nitrogen, the ntrC null mutants failed to adapt to new nutrient conditions and were slow to exit from the lag phase. Gene expression studies at lag phase showed down-regulation of the genes involved in carbon/nitrogen transportation and metabolism in {Delta}ntrC mutant. In the co-culture competition studies, we observed that ntrC knockout was unable to survive with the wild-type Salmonella and E. coli. We also observed that the {Delta}ntrC mutant did not survive long term nitrogen starvation (150 days). Critical analysis of starvation survival revealed that, ntrC gene is essential for recycling of nutrients from the dead cells. The nutrient recycling efficiency of {Delta}ntrC mutant was [~] 12 times less efficient than wild-type. Hence, the current work establishes that ntrC expression at the lag phase is essential for competitive fitness of Salmonella to survive in an environment having low and fluctuating nutrient conditions. ImportanceSalmonella Typhimurium, both inside or outside of the host organism face enormous competition from other microorganisms. The competition may take place either in steady or in fluctuating climatic conditions. Thus, how Salmonella Typhimurium survive under such overlapping stress conditions, remained unclear. Therefore, here we report that, a global regulator NtrC, which is also a part of two-component system, activates the set of genes and operons involved in rapid adaptation and efficient nutrient recycling/scavenging. These properties, make cell able to compete with other microbes, under characteristic feast- or-famine life style of Salmonella Typhimurium. Therefore, this piece of work helps us to understand the starvation physiology of enteric bacterial pathogen Salmonella Typhimurium.