However, the prevalence and genetic diversity of hypermutator isolates obtained from patients with CF in Australia have received much less attention. aeruginosa hypermutators in isolates from patients with CF has been examined across several clinics in Europe (15% to 54% average, 27%) ( 4, 7, 8, 10, 26, – 29) and the Americas (17% to 42% average, 29%) ( 9, 30, 31). These phenotypic changes may occur more readily in hypermutator strains due to the increased mutation rates. Common mutation-mediated antibiotic resistance mechanisms include the increased expression of Mex-efflux pumps following mutations in regulator genes ( 21, – 23), antibiotic-binding-site modifications ( 24), increased production of antibiotic inactivating β-lactamase enzymes ( 25), and inactivation of outer membrane porins that lead to cell membrane permeability changes and reduced intracellular drug accumulation ( 23).
aeruginosa cells show a variety of diverse phenotypic changes associated with adaptation to the CF lung, including conversion to a mucoid phenotype ( 13, 14), inactivation of quorum-sensing functions ( 15, – 17), motility loss ( 18, 19), and various auxotrophies ( 20). Mutations in the 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG or GO) system genes, mutM, mutY, and mutT, have also been found to produce the hypermutator phenotype in P. The hypermutator phenotype results from the mutation of genes involved in DNA repair, especially genes involved in the mismatch repair (MMR) system ( mutS, mutL, and uvrD) ( 10, 11). aeruginosa strains can quickly adapt to antibiotic exposure ( 4), and these strains have been strongly linked with antibiotic resistance within patients with CF ( 3, 4, 6, 7). These hypermutators show an increased mutation rate of up to 1,000-fold compared to that of wild-type strains ( 6) and this, together with the short bacterial generation time, allows them to rapidly adapt to a variety of stressful environments ( 9). aeruginosa strains ( 3, – 6), a finding generally associated with poorer patient outcomes ( 7, 8). Patients with CF have frequently been found to harbor hypermutable P. Pseudomonas aeruginosa frequently causes chronic pulmonary infections that are associated with increased morbidity and mortality among patients with suppurative lung diseases, especially those with cystic fibrosis (CF) ( 1, 2). aeruginosa strains are common among isolates from patients with CF in Australia and are implicated in the emergence of antibiotic resistance. Multidrug resistance was more prevalent in hypermutable than nonhypermutable isolates (38% versus 22%). Hypermutable isolates also contained a range of mutations that are likely associated with adaptation of P. Phylogenetic analyses showed that the hypermutators were from divergent lineages and that hypermutator phenotype was mostly the result of mutations in mutL or, less commonly, in mutS. Core genome polymorphisms were used to assess genetic relatedness of the isolates, both to each other and to a sample of previously characterized P. Whole-genome sequences were determined for all hypermutable isolates. Of the 59 isolates, 13 (22%) were hypermutable. For all isolates, rifampin (RIF) mutation frequencies and susceptibility to a range of antibiotics were determined. aeruginosa clinical isolates from patients with CF were characterized. aeruginosa isolates from adult patients with CF from a health care institution in Australia and to characterize the genetic diversity and antibiotic susceptibility of these isolates. This study aimed to determine the prevalence of hypermutable P. Their prevalence has been established among patients with CF, but it has not been determined for patients with CF in Australia. Hypermutators display a greatly increased mutation rate and an enhanced ability to become resistant to antibiotics during treatment. Hypermutable Pseudomonas aeruginosa isolates (hypermutators) have been identified in patients with cystic fibrosis (CF) and are associated with reduced lung function.
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