Functional OmpA of Salmonella Typhimurium Provides Protection From Lysosomal Degradation and Inhibits Autophagic Processes in Macrophages.

Abstract

Our previous study showed that OmpA-deficient Salmonella Typhimurium failed to retain LAMP-1 around the Salmonella-containing vacuoles (SCV), and escaped in to the host cell cytosol. Here we show that the cytosolic population of S. Typhimurium ΔompA sequestered autophagic markers, syntaxin17 and LC3B, in a sseL-dependent manner and initiated lysosomal fusion. Moreover, inhibition of autophagy using bafilomycinA1 restored its intracellular proliferation. Ectopic overexpression of OmpA in S. Typhimurium ΔsifA restored its vacuolar niche and increased its interaction with LAMP-1, suggesting a sifA-independent role of OmpA in maintaining an intact SCV. Mutations in the OmpA extracellular loops impaired the LAMP-1 recruitment to SCV and caused bacterial release into the cytosol of macrophages, but unlike S. Typhimurium ΔompA, they retained their outer membrane stability and did not activate the lysosomal degradation pathway, aiding in their intramacrophage survival. Finally, OmpA extracellular loop mutations protected cytosolic S. Typhimurium ΔsifA from lysosomal surveillance, revealing a unique OmpA-dependent strategy of S. Typhimurium for its intracellular survival.