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.

Highlights

  • Outer membrane vesicles (OMVs) are nanospherical proteoliposomes (20–400 nm diameter) continually released from the outer membrane of all Gram-negative bacteria [1, 2]

  • Compared to WT, the PT6SS1::lacZ promoter activity was significantly increased in the Δfur mutant, and this increase could be restored by introducing the complementary plasmid pBBR1MCS-5-fur (Fig. 1B)

  • These results demonstrate that the expression of T6SS1 in C. necator is directly repressed by Fur, the master regulator of genes involved in iron homeostasis in many prokaryotes [40, 41]

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Summary

Introduction

Outer membrane vesicles (OMVs) are nanospherical proteoliposomes (20–400 nm diameter) continually released from the outer membrane of all Gram-negative bacteria [1, 2]. They are primarily composed of outer membrane proteins, phospholipids, and lipopolysaccharides (LPSs), and are filled with periplasmic and cytoplasmic components such as peptidoglycan, proteins, nucleic acids, quorum sensing (QS) signals, and metal ions in the vesicle lumen [3,4,5]. OMVs have shown great potential as vaccine platform [19, 20] and drug delivery vehicles for cancer therapy [21, 22]

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