Type VI secretion system MIX-effectors carry both antibacterial and anti-eukaryotic activities

EMBO Rep. 2017 Nov;18(11):1978-1990. doi: 10.15252/embr.201744226. Epub 2017 Sep 14.

Abstract

Most type VI secretion systems (T6SSs) described to date are protein delivery apparatuses that mediate bactericidal activities. Several T6SSs were also reported to mediate virulence activities, although only few anti-eukaryotic effectors have been described. Here, we identify three T6SSs in the marine bacterium Vibrio proteolyticus and show that T6SS1 mediates bactericidal activities under warm marine-like conditions. Using comparative proteomics, we find nine potential T6SS1 effectors, five of which belong to the polymorphic MIX-effector class. Remarkably, in addition to six predicted bactericidal effectors, the T6SS1 secretome includes three putative anti-eukaryotic effectors. One of these is a MIX-effector containing a cytotoxic necrotizing factor 1 domain. We demonstrate that T6SS1 can use this MIX-effector to target phagocytic cells, resulting in morphological changes and actin cytoskeleton rearrangements. In conclusion, the V. proteolyticus T6SS1, a system homologous to one found in pathogenic vibrios, uses a suite of polymorphic effectors that target both bacteria and eukaryotic neighbors.

Keywords: Vibrio; CNF1; bacterial competition; virulence.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / toxicity
  • Aquatic Organisms
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / toxicity
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / toxicity
  • Chromosome Mapping
  • Chromosomes, Bacterial / chemistry*
  • Coculture Techniques
  • Escherichia coli / drug effects
  • Escherichia coli / growth & development
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Escherichia coli Proteins / toxicity
  • Gene Expression Regulation, Bacterial*
  • Mice
  • Phagocytes / cytology
  • Phagocytes / drug effects
  • Protein Domains
  • RAW 264.7 Cells
  • Type VI Secretion Systems / chemistry
  • Type VI Secretion Systems / genetics*
  • Type VI Secretion Systems / metabolism
  • Vibrio / genetics*
  • Vibrio / metabolism
  • Vibrio / pathogenicity
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Escherichia coli Proteins
  • Type VI Secretion Systems
  • cytotoxic necrotizing factor type 1