Comparative genomics of ocular Pseudomonas aeruginosa strains from keratitis patients with different clinical outcomes

Abstract

Bacterial keratitis caused by Pseudomonas aeruginosa is a destructive disease of cornea. Pseudomonas keratitis progresses rapidly and leads to vision loss if untreated. Even with adequate treatment, many patients show poor visual outcomes. The virulence factors or multiple drug-resistant (MDR) mechanisms of the ocular strains responsible for poor clinical outcomes remain largely unknown. Here, we performed whole-genome sequencing of five P. aeruginosa strains cultured from corneal scrapings of the healed and corneal buttons of the poor outcome keratitis patients. We investigated the distribution of virulence factors, resistance genes and resistance-associated mutations, the efflux-pump system in all five genomes, and as groups between poor and good clinical outcome as well as MDR vs. non-MDR. We detected several resistance genes and mutations associated with drug resistance in MDR groups; however, a large number of virulence genes were detected in all our genomes. Among the virulence genes, exoU and exoS exotoxin of the Type III secretion system detected in MDR and non-MDR strains, respectively, considered as main virulence contributors of keratitis pathogenesis. Despite this fact, this study did not show an association between MDR with exoU and poor clinical outcomes. However, strain-specific resistance and virulence genes were observed in this study, suggesting their role in the clinical outcome. Mainly, the flagellar genes fliC and fliD, reported to altering the host immune response, might impact the clinical outcome. This comparative study may provide new insights into the genome of ocular strains and requires further functional studies.