Type IV secretion in Gram‐negative and Gram‐positive bacteria

Abstract

Summary Type IV secretion systems (T4SSs) are versatile multiprotein nanomachines spanning the entire cell envelope in Gram‐negative and Gram‐positive bacteria. They play important roles through the contact‐dependent secretion of effector molecules into eukaryotic hosts and conjugative transfer of mobile DNA elements as well as contact‐independent exchange of DNA with the extracellular milieu. In the last few years, many details on the molecular mechanisms of T4SSs have been elucidated. Exciting structures of T4SS complexes from Escherichia coli plasmids R388 and pKM101, Helicobacter pylori and Legionella pneumophila have been solved. The structure of the F‐pilus was also reported and surprisingly revealed a filament composed of pilin subunits in 1:1 stoichiometry with phospholipid molecules. Many new T4SSs have been identified and characterized, underscoring the structural and functional diversity of this secretion superfamily. Complex regulatory circuits also have been shown to control T4SS machine production in response to host cell physiological status or a quorum of bacterial recipient cells in the vicinity. Here, we summarize recent advances in our knowledge of ‘paradigmatic’ and emerging systems, and further explore how new basic insights are aiding in the design of strategies aimed at suppressing T4SS functions in bacterial infections and spread of antimicrobial resistances.

Reactive oxygen species‐mediated endoplasmic reticulum stress response induces apoptosis ofMycobacterium avium‐infected macrophages by activating regulated IRE1‐dependent decay pathway

“…A previous study has demonstrated that the RIDD pathway promotes inflammation and apoptosis via the NLRP3 inflammasome (Lerner et al, ). A recent report suggests that activation of the IRE1 pathway plays an important role in removing Brucella abortus by inducing a proinflammatory response in macrophages (Grohmann, Christie, Waksman, & Backert, ). These findings provide clues to support our results why IRE1α‐RIDD pathway activation is involved in suppression of M. avium growth in macrophages.…”

Biological Diversity and Evolution of Type IV Secretion Systems

“…Perhaps one of the most intriguing mysteries surrounding type IV secretion is the route(s) by which substrates are conveyed across the cytoplasmic membrane (Grohmann et al 2018). Based on available structure—function information summarized above for the T4ASS and T4BSS transporters, three possible translocation routes can be envisioned: (1) substrates pass directly through the lumen of the VirD4 hexamer, (2) substrates are transferred to the VirB4 hexamer for delivery through its central channel, or (3) after engaging with the ATPases for processing/unfolding, substrates pass through a channel composed of IMC subunits, e.g., VirB6 and VirB8 (Fig.…”

“…The T4SSs are widely distributed among gram-negative (Gram − ) and gram-positive (Gram + ) bacteria, and they mediate a broad range of functions to the benefit of their bacterial hosts (Grohmann et al 2018). Various schemes have emerged to classify T4SSs, an undertaking complicated by the extreme genetic and functional heterogeneity of this secretion superfamily.…”

A novel T4SS‐mediated DNA transfer used by pXO16, a conjugative plasmid from Bacillus thuringiensis serovar israelensis

“…In spite of the limited knowledge on Gram-positive systems, it is suggested that their transfer systems are mechanistically and structurally similar to Gram-negative ones. Yet, because of the absence of conjugative pili and the obvious differences in cell envelopes to be crossed, Gram-positive bacteria are expected to encode 'simpler' T4SS-like structures (Alvarez-Martinez and Christie, 2009;Grohmann et al, 2017).…”