Interspecies Crosstalk via LuxI/LuxR-Type Quorum Sensing Pathways Contributes to Decreased Nematode Survival in Coinfections of Pseudomonas aeruginosa and Burkholderia multivorans

Quorum sensing (QS) is a prominent chemical communication mechanism used by common bacteria to regulate group behaviors at high cell density, including many processes important in pathogenesis. There is growing evidence that certain bacteria can use QS to sense not only themselves but also other species and that this crosstalk could alter collective behaviors. In the current study, we report the results of culture-based and in vivo coinfection experiments that probe interspecies interactions between the opportunistic pathogens Pseudomonas aeruginosa and Burkholderia multivorans involving their LuxI/LuxR-type QS circuits. Using a Caenorhabditis elegans infection model, we show that infections with both species result in poorer host outcomes compared with monoinfections. We use genetic mutants and a transwell infection assay to establish that crosstalk via LuxR-type receptors and signals is important for this coinfection pathogenicity. Using laboratory cocultures with cell-based reporter systems, we show that the RhlR and CepR receptors in P. aeruginosa and B. multivorans, respectively, can each recognize a QS signal produced by the other species. Lastly, we apply chemical biology to complement our genetic approach and demonstrate the potential to regulate interspecies interactions between the wild-type strains of P. aeruginosa and B. multivorans through the application of synthetic compounds that modulate RhlR and CepR activities. Overall, this study reveals that interspecies interaction via QS networks is possible between P. aeruginosa and B. multivorans and that it can contribute to coinfection severity with these two species.