Abstract
Staphylococcus aureus is next to Pseudomonas aeruginosa the most isolated pathogen from the airways of cystic fibrosis (CF) patients, who are often infected by a dominant S. aureus clone for extended periods. To be able to persist, the pathogen has to adapt to the hostile niche of the airways to counteract host defence, antibiotic therapy and the competition with coinfecting pathogens. S. aureus is equipped with many virulence factors including adhesins, toxins that are localized on the chromosome, on plasmids or are phage-related. S. aureus is especially versatile and adaptation and evolution of the pathogen occurs by the acquisition of new genes by horizontal gene transfer (HGT), changes in nucleotides (single nucleotide variations, SNVs) that can cause a selective advantage for the bacteria and become fixed in subpopulations. Methicillin-resistant S. aureus are a special threat to CF patients due to the more severe lung disease occurring in infected patients. Today, with decreasing costs for sequencing, more and more studies using S. aureus isolates cultured from CF patients are being published, which use whole genome sequencing (WGS), multilocus sequence typing (MLST) or spa-sequence typing (spa-typing) to follow the population dynamics of S. aureus, elucidate the underlying mechanisms of phenotypic variants, newly acquired resistance or adaptation to the host response in this particular niche. In the first part of this review, an introduction to the genetic make-up and the pathogenesis of S. aureus with respect to CF is provided. The second part presents an overview of recent studies and their findings using genotypic methods such as single or multilocus sequencing and whole genome sequencing, which identify factors contributing to the adaptation of S. aureus and its evolution in the airways of individuals with CF.
Highlights
Adaptation to cystic fibrosis (CF) AirwaysPersistent S. aureus clones tend to form a genetically (and especially phenotypically) heterogeneous population [15]
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We aimed to summarize the results of all the available studies that used whole genome sequencing (WGS) of S. aureus cystic fibrosis (CF) isolates to address a variety of research questions such as determining population dynamics, confirming the persistence of a single S. aureus lineage during chronic infection, elucidating the patho-adaptation during persistence, identifying the underlying mechanisms of metabolic or phenotypic changes, or new resistance mechanisms
Summary
Persistent S. aureus clones tend to form a genetically (and especially phenotypically) heterogeneous population [15]. The agr systems contain a variable region in AgrC, which allows the differentiation of four different agr types, which correlate with certain, toxin-mediated diseases; for instance, agr-type 3 associates with toxic shock syndrome (TSS) and agr-type 4 with staphylococcal scalded skin syndrome (SSSS) [54]. It remains unclear whether differing activities of the agr-types are the main causative factor determining this association or whether different agr-types are merely an indicator of a certain clonal background, that for its part accounts for the occurrence of the respective syndromes [45,54]. In accordance with those correlations, it has been found that the agr-system is often inactive in CF airways, which provides a perfect example of the above-mentioned chronic, localized infection [31,57]
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