T6SS secretes an LPS-binding effector to recruit OMVs for exploitative competition and horizontal gene transfer

Abstract

Outer membrane vesicles (OMVs) can function as nanoscale vectors that mediate bacterial interactions in microbial communities. How bacteria recognize and recruit OMVs inter-specifically remains largely unknown, thus limiting our understanding of the complex physiological and ecological roles of OMVs. Here, we report a ligand-receptor interaction-based OMV recruitment mechanism, consisting of a type VI secretion system (T6SS)-secreted lipopolysaccharide (LPS)-binding effector TeoL and the outer membrane receptors CubA and CstR. We demonstrated that Cupriavidus necator T6SS1 secretes TeoL to preferentially associate with OMVs in the extracellular milieu through interactions with LPS, one of the most abundant components of OMVs. TeoL associated with OMVs can further bind outer membrane receptors CubA and CstR, which tethers OMVs to the recipient cells and allows cargo to be delivered. The LPS-mediated mechanism enables bacterial cells to recruit OMVs derived from different species, and confers advantages to bacterial cells in iron acquisition, interbacterial competition, and horizontal gene transfer (HGT). Moreover, our findings provide multiple new perspectives on T6SS functionality in the context of bacterial competition and HGT, through the recruitment of OMVs.

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics

“… 99 H3-T6SS secrete TseF to facilitate the import of the PQS-Fe 3+ complex into cells by incorporating it into OMVs with Pseudomonas quinolone signal (PQS). 100 Interestingly, it was found that the quorum sensing (QS) system plays an important role in the expression of this secretion system. In P. aeruginosa , QS differentially regulates three loci of encoding T6SS (HSI-I, HSI-II, and HSI-III) by LasR and MvfR.…”

Outer membrane vesicles as molecular biomarkers for Gram-negative sepsis: Taking advantage of nature’s perfect packages

“…Recently, some groups have successfully isolated human EVs by targeting specific phospholipids using Tim4 protein and annexin V ( 115 , 130 ). Similarly, anti-LPS or LPS-binding effector TeoL could be used to isolate LPS-rich OMVs ( 131 ). Additionally, some are investigating whether proteins that sense and bind to highly curved phospholipid membranes and the peptides derived from them can be used to selectively capture EVs ( 132 , 133 ).…”

Roles of Type VI Secretion System in Transport of Metal Ions

“…The H3-T6SSpromoters and tseF expression for iron acquisition are commonly repressed by the ferric uptake regulator (Fur) for intracellular iron homeostasis (Lin et al, 2017). In Cupriavidus necator, T6SS1 secreted TeoL preferentially in association with OMVs through interactions with LPS, which enables bacterial cells to recruit OMVs derived from different species and confers advantages to bacterial cells for iron acquisition (Li et al, 2021).…”