Characterization of hypermutator Pseudomonas aeruginosa isolates from patients with cystic fibrosis in Australia [Mechanisms of Resistance]

Hypermutable Pseudomonas aeruginosa isolates (hypermutators) have been identified in patients with cystic fibrosis (CF). Hypermutators display a greatly increased mutation rate, an enhanced ability to become resistant to antibiotics during treatment and are associated with reduced lung function in patients. Their prevalence has been established amongst patients with CF, but has not been determined for patients with CF in Australia. This study aimed to determine the prevalence of hypermutable P. aeruginosa isolates from adult patients with CF from a healthcare institution in Australia, and to characterize the genetic diversity and antibiotic susceptibility of these isolates. A total of 59 P. aeruginosa clinical isolates from patients with CF were characterized. For all isolates, rifampicin mutation frequencies and susceptibility to a range of antibiotics were determined. Of the 59 isolates, 13 (22%) were hypermutable. Whole genome sequences were determined for all hypermutable isolates. Core genome polymorphisms were used to assess genetic relatedness of the isolates, both to each other and to a sample of previously characterized P. aeruginosa strains. Phylogenetic analyses showed that the hypermutators were from divergent lineages and hypermutator phenotype was mostly the result of mutations in mutL, or less commonly mutS. Hypermutable isolates also contained a range of mutations likely associated with adaptation of P. aeruginosa to the CF lung environment. Multidrug-resistance was greater for hypermutable than non-hypermutable isolates (38% vs. 22%). This study revealed that hypermutable P. aeruginosa are common among isolates from patients with CF in Australia and are implicated in the emergence of antibiotic resistance.

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