Rab32 restriction of intracellular bacterial pathogens

Abstract

Our immune system is engaged in a continuous battle against invading pathogens, many of which have evolved to survive in intracellular niches of mammalian hosts. A variety of cellular processes are involved in preventing bacterial invasion or in killing bacteria that successfully invade host cells. Recently, the Rab GTPase Rab32 emerged as critical regulator of a host defense pathway that can eliminate bacterial pathogens. Salmonella enterica is an intracellular bacterium and a major cause of infections and deaths in humans. Rab32 and its guanine nucleotide exchange factor BLOC-3 are essential to prevent the growth of the human-restricted Salmonella enterica serovar Typhi (S. Typhi) in mice, a non-susceptible host. The importance of the Rab32/BLOC-3 pathway has been recently confirmed by the finding that broad-host Salmonella enterica serovars deliver 2 bacterial effectors to neutralize this pathway and infect mice. Rab32 has also been shown to control infection by Listeria monocytogenes, another medically relevant intracellular pathogen. In addition, genetic evidence indicate a possible role of Rab32 in controlling leprosy, a disease caused by Mycobacterium leprae in humans, suggesting that a Rab32-dependent pathway can also act as a host defense pathway in humans. The Rab32 role in bacterial pathogen restriction is discussed here and compared to the function of this GTPase in other cellular processes.