Abstract
Pseudomonas aeruginosa, an opportunistic pathogen, uses a trio of quorum sensing (QS) systems to regulate the production of some virulence factors. Two of these, the las and rhl systems, involve acyl-homoserine lactone signals; the third, called pqs, primarily uses the signal 2-heptyl-3-hydroxy-4(1H)-quinolone ("PQS"). We aimed to identify how interbacterial interactions are regulated between P. aeruginosa and Stenotrophomonas maltophilia, which co-occur in the airways of people with cystic fibrosis. We explored P. aeruginosa and S. maltophilia interactions using a co-culture model. S. maltophilia in co-culture with P. aeruginosa grows for 12 hours and thereafter exhibits a large decline in CFU, demonstrating that P. aeruginosa is killing S. maltophilia. Co-culture of S. maltophilia with P. aeruginosa deficient in las, rhl, or pqs QS resulted in greater S. maltophilia viability than co-culture with the wildtype. This inhibition was not attributable to las and rhl-regulated toxins. Therefore, we interrogated the role of PQS and found that co-culture of S. maltophilia with P. aeruginosa deficient in PQS biosynthesis showed similar CFUs to monoculture. Exogenous PQS did not complement this phenotype, suggesting that another quinolone is the effector. We found that S. maltophilia killing is reduced in competition with a mutant that cannot make the quinolone HQNO. We show that full killing of S. maltophilia by P. aeruginosa requires three components: HQNO, the chaperone PqsE, and intact PQS biosynthesis. Our work identifies quinolone biosynthesis as a driver for interactions between P. aeruginosa and S. maltophilia and, more generally, in modulating interbacterial interactions.