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

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 Delta ompA 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 Delta sifA 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 Delta ompA, 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 Delta sifA from lysosomal surveillance, revealing a unique OmpA-dependent strategy of S. Typhimurium for its intracellular survival. Salmonella Typhimurium employs OmpA extracellular loops to interact with LAMP-1 and maintain intact SCV. The OmpA deletion but not mutations in its extracellular loop compromises the outer membrane stability and activates lysosomal degradation of cytosolic S. Typhimurium.