Exploring the role of quorum sensing and quorum sensing inhibition in the biotherapeutic potential of bacteria

摘要

The involvement of quorum sensing (QS) in several pathogenic bacteria to control biofilm formation and the expression of their virulence factors makes interfering with QS (QSI) a promising new antipathogenic strategy. To date, many components with QS inhibitory properties have been characterized, but the majority of these compounds are not useful in vivo. The specific aim of this study was to explore the potential of interfering with QS by other, potentially biotherapeutic bacteria. First we developed a high-throughput method for the isolation of QSI bacteria from environmental samples. Further experiments with these isolates demonstrated that some of these them produce and secrete heat-stable, low molecular weight QSI compounds, whereas others degrade QS signaling molecules enzymatically. In a second study we assessed the biotherapeutic potential of these isolates in vitro and in vivo. We showed that certain isolates with QSI properties are able to inhibit biofilm formation of the P. aeruginosa PAO1. Another observation was that some of the isolates decrease elastase production by P. aeruginosa PAO1. Finally, administration of various QSI isolates to infected nematodes resulted in an increased survival. Together, these data confirm the biotherapeutic potential of certain environmental isolates. In addition to organisms producing QSI compounds, we also observed that a functional luxS gene is widespread in bifidobacteria, which are commonly regarded as beneficial microbes. This gene encodes the synthase of the QS signaling molecule AI-2, and is generally linked to virulence and pathogenicity. However, our findings showed that LuxS plays a crucial role in gut colonization and probiotic functionality of bifidobacteria, most likely via a mechanism affecting iron metabolism. These data contributed to the unraveling of the molecular mechanisms behind the beneficial effects of bifidobacteria.