Whole Genome Analysis of Ocular Pseudomonas aeruginosa Isolates Reveals Genetic Diversity

对眼部铜绿假单胞菌分离株的全基因组分析揭示了其遗传多样性

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Abstract

PURPOSE: Pseudomonas aeruginosa is a versatile pathogen and leading cause of ocular infections. Several large-scale analyses have identified epidemic clones of P. aeruginosa adapted to human infection, but few genomic studies have focused on ocular infection. We sought to determine whether specific clones of P. aeruginosa are associated with ocular infection and to characterize the pool of virulence factors and antibiotic resistance genes present in ocular isolates. METHODS: Ninety-two non-duplicate P. aeruginosa isolates from patients with ocular infections were collected in our service. Whole genome sequencing was completed followed by analysis of phylogeny, key virulence factors, and phenotypic and genotypic antibiotic resistance. RESULTS: We found genetic diversity among our isolates, with no predominant clonal group. Analysis of virulence factors showed that the majority of our isolates encode the exotoxin ExoS, in contrast to previous studies in which ocular isolates were predominantly ExoU-positive. We also found a high frequency of mutations in the quorum sensing receptors LasR and RhlR, adding to growing evidence that such mutations are common in multiple types of infection. Finally, we identified two isolates lacking genes for biofilm exopolysaccharide Psl biosynthesis, as well as within-host variation in alginate production. Consistent with the community origins of our isolates, we found a low rate of antibiotic resistance (<7%), with only two multidrug resistant isolates. CONCLUSIONS: Our study significantly increases the number of ocular P. aeruginosa genomes available for phylogenomic analyses and reveals that P. aeruginosa ocular infections at our institution are caused by a highly genetically diverse population.

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