Abstract
The genetic disorder cystic fibrosis is a life-limiting condition affecting ∼70,000 people worldwide. Targeted, early, treatment of the dominant infecting species, Pseudomonas aeruginosa, has improved patient outcomes; however, there is concern that other species are now stepping in to take its place. In addition, the necessarily long-term antibiotic therapy received by these patients may be providing a suitable environment for the emergence of antibiotic resistance. To investigate these issues, we employed whole-genome sequencing of 28 non-Pseudomonas bacterial strains isolated from three paediatric patients. We did not find any trend of increasing antibiotic resistance (either by mutation or lateral gene transfer) in these isolates in comparison with other examples of the same species. In addition, each isolate contained a virulence gene repertoire that was similar to other examples of the relevant species. These results support the impaired clearance of the CF lung not demanding extensive virulence for survival in this habitat. By analysing serial isolates of the same species we uncovered several examples of strain persistence. The same strain of Staphylococcus aureus persisted for nearly a year, despite administration of antibiotics to which it was shown to be sensitive. This is consistent with previous studies showing antibiotic therapy to be inadequate in cystic fibrosis patients, which may also explain the lack of increasing antibiotic resistance over time. Serial isolates of two naturally multi-drug resistant organisms, Achromobacter xylosoxidans and Stenotrophomonas maltophilia, revealed that while all S. maltophilia strains were unique, A. xylosoxidans persisted for nearly five years, making this a species of particular concern. The data generated by this study will assist in developing an understanding of the non-Pseudomonas species associated with cystic fibrosis.
Highlights
The impaired clearance of the respiratory tract of patients with cystic fibrosis (CF) permits chronic infection by microorganisms
The species present in CF patients has been observed to fluctuate with age; S. aureus and H. influenzae are more often associated with younger patients, while Stenotrophomonas maltophilia and P. aeruginosa increase in prevalence in older patients (Razvi et al, 2009; Cox et al, 2010)
P. aeruginosa has previously been identified as the primary disease causing agent (Høiby, 1982) and improved patient outcomes have been achieved through aggressive antibiotic therapy targeting this species during the early stages of disease prior to the establishment of chronic infection (Høiby, Frederiksen & Pressler, 2005)
Summary
The impaired clearance of the respiratory tract of patients with cystic fibrosis (CF) permits chronic infection by microorganisms (reviewed in Boucher, 2007). Pseudomonas aeruginosa and Staphylococcus aureus are the two most commonly isolated species (Emerson et al, 2010), with prevalence rates over 50% (Razvi et al, 2009). The species present in CF patients has been observed to fluctuate with age; S. aureus and H. influenzae are more often associated with younger patients, while Stenotrophomonas maltophilia and P. aeruginosa increase in prevalence in older patients (Razvi et al, 2009; Cox et al, 2010). P. aeruginosa has previously been identified as the primary disease causing agent (Høiby, 1982) and improved patient outcomes have been achieved through aggressive antibiotic therapy targeting this species during the early stages of disease prior to the establishment of chronic infection (Høiby, Frederiksen & Pressler, 2005). Life expectancy of CF patients has improved in recent years, still remains low at ∼40 years (Quon & Aitken, 2012)
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