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

Ann Ray,Junmei Zhang,Kim Orth,Dor Salomon,Marcela De Souza Santos,Nika Schwartz

doi:10.15252/embr.201744226

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.

Highlights

A common strategy used by bacteria to manipulate neighbors is to secrete proteins, termed toxins or effectors, via specialized protein secretion systems [1]
We found that of the three T6SSs encoded by Vpr, T6SS1 mediated antibacterial activities
The T6SS2 cluster is similar to the T6SS3 cluster in terms of gene content and organization, with two differences: (i) the genes encoding VgrG2PAAR2 are transcribed in the same direction as the rest of the cluster, whereas their counterparts in T6SS3 are inverted; (ii) the genes between clpV and fha differ between the clusters (Fig 1)

Summary

Introduction

A common strategy used by bacteria to manipulate neighbors is to secrete proteins, termed toxins or effectors, via specialized protein secretion systems [1]. To determine whether the bactericidal activity of Vpr is mediated by either of the T6SSs, we generated strains deleted for each of the three vgrG genes that correspond to the three T6SS clusters. The expression and secretion pattern of the secreted T6SS1 tail-tube spike component VgrG1 agreed with the level of Vpr bactericidal activity under the same conditions and peaked at 30°C in media containing 3% NaCl (Appendix Fig S1).

Results

Conclusion