Pseudomonas aeruginosa promotes persistence of Stenotrophomonas maltophilia via increased adherence to depolarized respiratory epithelium

Abstract

ABSTRACTStenotrophomonas maltophilia is an emerging opportunistic respiratory pathogen in patients with cystic fibrosis (CF). S. maltophilia is frequently observed in polymicrobial infections, and we have previously shown that Pseudomonas aeruginosa promotes colonization and persistence of S. maltophilia in mouse respiratory infections. In this study, we used host and bacterial RNA sequencing to further define this interaction. To evaluate S. maltophilia transcript profiles we used a recently described method for selective capture of bacterial mRNA transcripts with strain specific RNA probes. We found that factors associated with the type IV pilus, including the histidine kinase subunit of a chemotactic two-component signaling system (chpA), had increased transcript levels during polymicrobial infection. Using immortalized CF respiratory epithelial cells, we found that infection with P. aeruginosa increases adherence of S. maltophilia, at least in part due to disruption of epithelial tight junctions. In contrast, an isogenic S. maltophilia chpA mutant lacked cooperative adherence to CF epithelia and decreased bacterial burden in vivo in polymicrobial infections with P. aeruginosa. Similarly, P. aeruginosa lacking elastase (lasB) did not promote S. maltophilia adherence or bacterial colonization and persistence in vivo. Based on these results, we conclude that disruption of lung tissue integrity by P. aeruginosa promotes adherence of S. maltophilia to the lung epithelia in a type IV pilus-dependent manner. These data provide insight into S. maltophilia colonization and persistence in patients in later stages of CF disease and may have implications for interactions with other bacterial opportunists.IMPORTANCEDespite advances in treatment options for patients with cystic fibrosis (CF), complications of bacterial infections remain the greatest driver of morbidity and mortality in this patient population. These infections often involve more than one bacterial pathogen, and our understanding of how inter-species interactions impact disease progression is lacking. Previous work in our lab found that two CF pathogens, Stenotrophomonas maltophilia and Pseudomonas aeruginosa can cooperatively infect the lung to cause more severe infection. In the present study, we found that infection with P. aeruginosa promotes persistence of S. maltophilia by interfering with epithelial barrier integrity. Depolarization of the epithelial cell layer by P. aeruginosa secreted elastase increased S. maltophilia adherence, likely in a type IV pilus-dependent manner. Ultimately, this work sheds light on the molecular mechanisms governing an important polymicrobial interaction seen in pulmonary diseases such as CF.