A quorum-sensing molecule from <i>Pseudomonas aeruginosa</i> induces defensive multicellularity in a coinfecting pathogen.

Abstract

Microorganisms commonly exist in polymicrobial communities, where they can respond to interspecies secreted molecules by altering behaviors and physiology; however, the underlying mechanisms remain underexplored. Here, we investigated interactions between <i>Stenotrophomonas maltophilia</i> and <i><i>Pseudomonas aeruginosa</i></i>, coinfecting opportunistic pathogens found in pneumonia and chronic lung infections, such as in cystic fibrosis. We found that <i>S. maltophilia</i> forms large protective multicellular aggregates upon exposure to <i><i>P. aeruginosa</i></i> secreted factors. Experimental evolution for lack of aggregation selected for fimbrial mutations and we found that fimbriae are required on both interacting <i>S. maltophilia</i> cells for aggregation. Untargeted metabolomics and targeted validations revealed that the quorum-sensing molecule <i><i>Pseudomonas</i></i> quinolone signal (PQS) directly induced <i>S. maltophilia</i> aggregation, and colocalized with the aggregates. Further, in coculture with <i><i>P. aeruginosa</i></i>, wild-type <i>S. maltophilia</i> formed aggregates, resulting in up to 75-fold increased survival from <i><i>P. aeruginosa</i></i> competition compared to fimbrial mutants. Finally, multiple other bacterial species similarly aggregated upon exposure to <i><i>P. aeruginosa</i></i> PQS, indicating a more general response. Collectively, our work identifies a multispecies interaction where a quorum-sensing molecule from a coinfecting pathogen is sensed as a "danger" signal, thereby inducing a protective multicellular response.