Interspecies\nCrosstalk via LuxI/LuxR-Type Quorum Sensing\nPathways Contributes to Decreased Nematode Survival in Coinfections\nof Pseudomonas aeruginosa and Burkholderia multivorans

Quorum sensing (QS) is a prominent chemical communication\nmechanism\nused by common bacteria to regulate group behaviors at high cell density,\nincluding many processes important in pathogenesis. There is growing\nevidence that certain bacteria can use QS to sense not only themselves\nbut also other species and that this crosstalk could alter collective\nbehaviors. In the current study, we report the results of culture-based\nand <i>in vivo</i> coinfection experiments that probe interspecies\ninteractions between the opportunistic pathogens Pseudomonas\naeruginosa and Burkholderia multivorans involving their LuxI/LuxR-type QS circuits. Using a Caenorhabditis elegans infection model, we show that\ninfections with both species result in poorer host outcomes compared\nwith monoinfections. We use genetic mutants and a transwell infection\nassay to establish that crosstalk via LuxR-type receptors and signals\nis important for this coinfection pathogenicity. Using laboratory\ncocultures with cell-based reporter systems, we show that the RhlR\nand CepR receptors in P. aeruginosa and B. multivorans, respectively,\ncan each recognize a QS signal produced by the other species. Lastly,\nwe apply chemical biology to complement our genetic approach and demonstrate\nthe potential to regulate interspecies interactions between the wild-type\nstrains of P. aeruginosa and B. multivorans through the application of synthetic\ncompounds that modulate RhlR and CepR activities. Overall, this study\nreveals that interspecies interaction via QS networks is possible\nbetween P. aeruginosa and B. multivorans and that it can contribute to coinfection\nseverity with these two species.