Journal Article

Identification of divergent type VI secretion effectors using a conserved chaperone domain

Liang, Xiaoye, Megan J. Q. Wong, Mike Wilton, Tao G. Dong, Linh Lam, Richard Moore

2015

Overview

The type VI secretion system (T6SS) is a lethal weapon used by many bacteria to kill eukaryotic predators or prokaryotic competitors. Killing by the T6SS results from repetitive delivery of toxic effectors. Despite their importance in dictating bacterial fitness, systematic prediction of T6SS effectors remains challenging due to high effector diversity and the absence of a conserved signature sequence. Here, we report a class of T6SS effector chaperone (TEC) proteins that are required for effector delivery through binding to VgrG and effector proteins. The TEC proteins share a highly conserved domain (DUF4123) and are genetically encoded upstream of their cognate effector genes. Using the conserved TEC domain sequence, we identified a large family of TEC genes coupled to putative T6SS effectors in Gram-negative bacteria. We validated this approach by verifying a predicted effector TseC in Aeromonas hydrophila . We show that TseC is a T6SS-secreted antibacterial effector and that the downstream gene tsiC encodes the cognate immunity protein. Further, we demonstrate that TseC secretion requires its cognate TEC protein and an associated VgrG protein. Distinct from previous effector-dependent bioinformatic analyses, our approach using the conserved TEC domain will facilitate the discovery and functional characterization of new T6SS effectors in Gram-negative bacteria. How different microbial species compete for specific niches is not fully understood. Here, we focus on the type VI secretion system (T6SS), a specialized protein delivery system, which many Gram-negative bacteria use to kill eukaryotic and prokaryotic competitors by translocating toxic protein molecules to target cells. Identification of effectors is required for understanding the pivotal role that the T6SS plays in dictating interbacterial and bacterial–host dynamics. In this study, we describe a new approach to systematically identify T6SS effectors. We also demonstrate that secretion of effectors requires interaction with a set of cognate effector-binding chaperone proteins that we define in this study, providing important insights for understanding the mechanism of T6SS effector delivery.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Aeromonas - drug effects / Aeromonas - metabolism / Anti-Bacterial Agents - pharmacology / antitoxin / Bacteria / Bacterial Proteins - chemistry / Bacterial Proteins - metabolism / Bacterial Secretion Systems / Biological Sciences / colicin / Conserved Sequence / Eukaryotes / Genes / Gram-negative bacteria / Immunity - drug effects / interspecies interaction / Molecular Chaperones - chemistry / Molecular Chaperones - metabolism / niches / Predators / Protein Binding - drug effects / protein secretion / Protein Structure, Tertiary / Proteins / secretion / toxicity / toxin / type VI secretion system / Vibrio cholerae - drug effects / Vibrio cholerae - metabolism