A pore-forming toxin enables Serratia a nonlytic egress from host cells

Cell Microbiol. 2017 Feb;19(2). doi: 10.1111/cmi.12656. Epub 2016 Sep 23.

Abstract

Several pathogens co-opt host intracellular compartments to survive and replicate, and they thereafter disperse progeny to prosper in a new niche. Little is known about strategies displayed by Serratia marcescens to defeat immune responses and disseminate afterwards. Upon invasion of nonphagocytic cells, Serratia multiplies within autophagosome-like vacuoles. These Serratia-containing vacuoles (SeCV) circumvent progression into acidic/degradative compartments, avoiding elimination. In this work, we show that ShlA pore-forming toxin (PFT) commands Serratia escape from invaded cells. While ShlA-dependent, Ca2+ local increase was shown in SeCVs tight proximity, intracellular Ca2+ sequestration prevented Serratia exit. Accordingly, a Ca2+ surge rescued a ShlA-deficient strain exit capacity, demonstrating that Ca2+ mobilization is essential for egress. As opposed to wild-type-SeCV, the mutant strain-vacuole was wrapped by actin filaments, showing that ShlA expression rearranges host actin. Moreover, alteration of actin polymerization hindered wild-type Serratia escape, while increased intracellular Ca2+ reorganized the mutant strain-SeCV actin distribution, restoring wild-type-SeCV phenotype. Our results demonstrate that, by ShlA expression, Serratia triggers a Ca2+ signal that reshapes cytoskeleton dynamics and ends up pushing the SeCV load out of the cell, in an exocytic-like process. These results disclose that PFTs can be engaged in allowing bacteria to exit without compromising host cell integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • CHO Cells
  • Calcium / metabolism
  • Calcium Signaling
  • Cations, Divalent / metabolism
  • Cricetinae
  • Cricetulus
  • Cytoskeleton / metabolism
  • Exocytosis*
  • Hemolysin Proteins / metabolism*
  • Pore Forming Cytotoxic Proteins / metabolism*
  • Serratia marcescens / metabolism
  • Serratia marcescens / physiology*
  • Vacuoles / microbiology*

Substances

  • Bacterial Proteins
  • Cations, Divalent
  • Hemolysin Proteins
  • Pore Forming Cytotoxic Proteins
  • ShlA protein, Serratia marcescens
  • Calcium