Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals regions of diversity which correlate with colonization and persistence in vivo

Abstract

Stenotrophomonas maltophilia is a Gram-negative emerging opportunistic pathogen often found in respiratory diseases such as cystic fibrosis (CF). Patients with CF experience lifelong polymicrobial infections of the respiratory mucosa. Our prior work showed that P. aeruginosa promotes persistence of S. maltophilia mouse respiratory infections. As is typical for environmental opportunistic pathogens, S. maltophilia has a large genome and a high degree of genetic diversity. In this study, we evaluated the genomic content of S. maltophilia, combining short and long read sequencing to construct complete genomes of 10 clinical isolates which were then compared with the larger phylogeny of S. maltophilia genomic sequence data, and compared colonization/persistence in vivo, alone and in coinfection with P. aeruginosa. We found that while the overall genome size and GC content were fairly consistent, there was considerable variability in arrangement and gene content. Similarly, there was significant variability in S. maltophilia colonization and persistence in vivo in experimental mouse respiratory infection. Ultimately, this study gives us a greater understanding of the genomic diversity of S. maltophilia isolated from patients, and how this genomic diversity relates to interactions with other pulmonary pathogens, and to host disease progression. Identifying the molecular determinants of infection with S. maltophilia can facilitate development of novel antimicrobial strategies for a highly drug-resistant pathogen.