Transport mechanism of type VI secretion system effectors based on Hcp, VgrG , and PAAR components

Abstract

The type VI secretion system (T6SS) is a widespread contractile nanomachine in pathogenic bacteria that delivers diverse effectors directly into prokaryotic or eukaryotic target cells. These effectors confer competitive fitness advantages to attacker cells through multifaceted target manipulation. Current classification categorizes T6SS effectors as “specialized” or “cargo” types based on delivery mechanisms. This review systematically examines secretory pathways mediating effector translocation via covalent/non‐covalent interactions with the Hcp‐VgrG‐PAAR puncturing complex. Subsequently, it characterizes the distinctive features of Hcp‐, VgrG‐, and PAAR‐dependent effectors. In addition, this review highlights the indispensable role of adaptor proteins in effector‐core component recognition. By synthesizing the secretion modalities of diverse effectors via the T6SS puncturing structure, this review provides a comprehensive framework for understanding the loading and delivery mechanisms of T6SS effectors.