Host and bacterial proteins that repress recruitment of LC3 to Shigella early during infection

PLoS One. 2014 Apr 10;9(4):e94653. doi: 10.1371/journal.pone.0094653. eCollection 2014.

Abstract

Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4-6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autophagy / physiology*
  • Bacterial Proteins / metabolism*
  • Dysentery, Bacillary / microbiology*
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism
  • Shigella flexneri / metabolism*

Substances

  • Bacterial Proteins
  • Membrane Proteins