Host restriction in Salmonella: insights from Rab GTPases.

Salmonella enterica is a foodborne intracellular pathogen that can invade intestinal epithelial cells and survive in macrophages of susceptible hosts. Although belonging to the same species, individual Salmonella enterica serovars behave as very different pathogens. Indeed, they can cause very different diseases (from mild gastroenteritis to deadly systemic diseases) and have distinctive host selectivity. Salmonella enterica serovars Typhi (S. Typhi) is a unique serovar that has evolved to infect only humans and cause typhoid fever, a life-threatening systemic disease killing more than 200,000 people every year. The mechanisms that make S. Typhi able to infect only humans are mostly unknown. Recently, an antimicrobial traffic pathway dependent on the Rab GTPase Rab32 and its exchange factor BLOC-3 was found to be critical to kill S. Typhi in macrophages from non-susceptible hosts, suggesting that this pathway delivers an antimicrobial factor to the S. Typhi vacuole. Here we discuss this finding in the light of the current knowledge of pathogen killing mechanisms.