TheFrancisellaO-antigen mediates survival in the macrophage cytosol via autophagy avoidance

• DOI: 10.1111/cmi.12246
• Publication Date: 2013-11-29T09:46:49Z
• Authors: Elizabeth Di Russ...; Audrey Chong; Tara D. Wehrly; Bryan Hansen; Robert Child; Seungmin Hwang; Herbert W. Virgin; Jean Celli
• Keywords: Francisella; Intracellular parasite

Autophagy is a key innate immune response to intracellular parasites that promotes their delivery degradative lysosomes following detection in the cytosol or within damaged vacuoles. Like Listeria and Shigella, which use specific mechanisms avoid autophagic capture, bacterial pathogen Francisella tularensis proliferates of macrophages without demonstrable control by autophagy. To examine how evades autophagy, we screened library F. subsp. Schu S4 HimarFT transposon mutants GFP-LC3-expressing murine microscopy for clones localized vacuoles after phagosomal escape. Eleven showed capture at 6 h post-infection, whose insertions clustered fourgenetic loci involved lipopolysaccharidic capsular O-antigen biosynthesis. Consistent with mutants, in-frame deletion two representative loci, FTT1236 FTT1448c (manC), lacking both LPS O-antigen, underwent escape but were cleared from host cytosol. Unlike wild-type Francisella, ubiquitinated, recruited autophagy adaptor p62/SQSTM1 LC3 prior cytosolic clearance. Autophagy-deficient partially supported replication indicating O-antigen-lacking are controlled These data demonstrate protective role this surface polysaccharide against