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A Rab32-Dependent Pathway Contributes to Salmonella Typhi Host Restriction

Science  16 Nov 2012:
Vol. 338, Issue 6109, pp. 960-963
DOI: 10.1126/science.1229224

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Removing Typhoid Restriction

Some bacterial pathogens exhibit exquisite host adaptation and can only infect a single host. For example, Salmonella enterica serovar Typhi (S. Typhi), the cause of typhoid fever, can only infect humans. The host restriction is manifested at the cellular level because S. Typhi is unable to survive within macrophages of species other than human. Spanò and Galán (p. 960) found that expression of a single type-III secretion effector protein from a broad host Salmonella in S. Typhi, allowed this human-exclusive pathogen to survive within macrophages from a nonpermissive host. Furthermore, S. Typhi expressing this effector was able to replicate within mice, a nonpermissive host.

Abstract

Unlike other Salmonellae, the intracellular bacterial human pathogen Salmonella Typhi exhibits strict host specificity. The molecular bases for this restriction are unknown. Here we found that the expression of a single type III secretion system effector protein from broad-host Salmonella Typhimurium allowed Salmonella Typhi to survive and replicate within macrophages and tissues from mice, a nonpermissive host. This effector proteolytically targeted Rab32, which controls traffic to lysosome-related organelles in conjunction with components of the biogenesis of lysosome-related organelle complexes (BLOCs). RNA interference–mediated depletion of Rab32 or of an essential component of a BLOC complex was sufficient to allow S. Typhi to survive within mouse macrophages. Furthermore, S. Typhi was able to survive in macrophages from mice defective in BLOC components.

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