Bacterial produce membrane-binding small molecules to regulate horizontal gene transfer in vesicles

Abstract

The exchange of bacterial extracellular vesicles facilitates molecular exchange between cells, including the horizontal transfer of genetic material. Given the implications of such transfer events on cell physiology and adaptation, some bacterial cells have likely evolved mechanisms to regulate vesicle exchange. Past work has identified mechanisms that regulate the formation of extracellular vesicles, including the production of small molecules that modulate membrane structure, however whether these mechanisms also regulate vesicle uptake and have an overall impact on the rate of vesicle exchange is unknown. Here we show that membrane-binding molecules produced by microbes regulate both the formation and uptake of extracellular vesicles and have the overall impact of increasing the vesicle exchange rate within a bacterial coculture. In effect, production of compounds that influence vesicle exchange rates enable cells to steal genes from neighboring cells. The ability of several membrane-binding compounds to regulate vesicle exchange was demonstrated. Three of these compounds, nisin, colistin, and polymyxin B, are antimicrobial peptides added at sub-inhibitory concentrations. These results suggest that a key function of exogenous compounds that bind to membranes may be the regulation of vesicle exchange between cells. ImportanceThe exchange of bacterial extracellular vesicles is one route of gene transfer between bacteria, although it was unclear if bacteria developed strategies to regulate the rate of gene transfer within vesicles. In eukaryotes, there are many examples of specialized molecules that have evolved to facilitate the production, loading, and uptake of vesicles. Recent work with bacteria has shown that some small molecules influence membrane curvature and induce vesicle formation. Here we show that similar compounds facilitate vesicle uptake, thereby regulating the overall rate of vesicle exchange within bacterial populations. The addition of membrane-binding compounds, several of them antibiotics at sub-inhibitory concentrations, to a bacterial co-culture increased the rate of horizontal gene transfer via vesicle exchange.