Cooperativity between Stenotrophomonas maltophilia and Pseudomonas aeruginosa during Polymicrobial Airway Infections

Abstract

<i>Stenotrophomonas maltophilia</i> is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. <i>S. maltophilia</i> is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with <i>S. maltophilia</i> have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among <i>S. maltophilia</i> isolates, treatment options for these infections may be limited. Here, we investigated the pathogenicity of <i>S. maltophilia</i> alone and during polymicrobial infection with <i>Pseudomonas aeruginosa</i> Colonization, persistence, and virulence of <i>S. maltophilia</i> were assessed in experimental respiratory infections of mice. The results of this study indicate that <i>S. maltophilia</i> transiently colonizes the lung accompanied by significant weight loss and immune cell infiltration and the expression of early inflammatory markers, including interleukin 6 (IL-6), IL-1α, and tumor necrosis factor alpha (TNF-α). Importantly, polymicrobial infection with <i>P. aeruginosa</i> elicited significantly higher <i>S. maltophilia</i> counts in bronchoalveolar lavages and lung tissue homogenates. This increase in bacterial load was directly correlated with the density of the <i>P. aeruginosa</i> population and required viable <i>P. aeruginosa</i> bacteria. Microscopic analysis of biofilms formed <i>in vitro</i> revealed that <i>S. maltophilia</i> formed well-integrated biofilms with <i>P. aeruginosa</i>, and these organisms colocalize in the lung during dual-species infection. Based on these results, we conclude that active cellular processes by <i>P. aeruginosa</i> afford a significant benefit to <i>S. maltophilia</i> during polymicrobial infections. Furthermore, these results indicate that <i>S. maltophilia</i> may have clinical significance in respiratory infections.