Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals genetic diversity which correlates with colonization and persistence in vivo.

Stenotrophomonas maltophilia is a Gram-negative emerging opportunistic pathogen often present in people with respiratory diseases such as cystic fibrosis (CF). People with CF (pwCF) experience lifelong polymicrobial infections of the respiratory mucosa. Our prior work showed that Pseudomonas aeruginosa promotes persistence of S. maltophilia in 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 nearly complete genomes of 10 clinical isolates. The genomes of these isolates were then compared with all publicly available S. maltophilia genome assemblies, and each isolate was then evaluated for colonization/persistence in vivo, both alone and in coinfection with P. aeruginosa. We found that while the overall genome size and GC content were fairly consistent between strains, there was considerable variability in both genome structure and gene content. Similarly, there was significant variability in S. maltophilia colonization and persistence in experimental mouse respiratory infections in the presence or absence of P. aeruginosa. Ultimately, this study gives us a greater understanding of the genomic diversity of clinical S. maltophilia isolates, and how this genomic diversity relates to both 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.