Abstract
Staphylococcus aureus can colonize the human vestibulum nasi for many years. It is unknown whether and, how S. aureus adapts to this ecological niche during colonization. We determined the short (1 and 3 months) and mid-term (36 months) genomic evolution of S. aureus in natural carriers and artificially colonized volunteers. Eighty-five S. aureus strains were collected from 6 natural carriers during 3 years and 6 artificially colonized volunteers during 1 month. Multi-locus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis based on whole-genome sequencing (WGS) were carried out. Mutation frequencies within resident bacterial populations over time were quantified using core genome SNP counts (comparing groups of genomes) and pairwise SNP divergence assessment (comparing two genomes from strains originating from one host and sharing identical MLST). SNP counts (within 1–3 months) in all naturally colonizing strains varied from 0 to 757 (median 4). These strains showed random and independent patterns of pairwise SNP divergence (0 to 44 SNPs, median 7). When the different core genome SNP counts over a period of 3 years were considered, the median SNP count was 4 (range 0–26). Host-specific pairwise SNP divergence for the same period ranged from 9 to 57 SNPs (median 20). During short term artificial colonization the mutation frequency was even lower (0–7 SNPs, median 2) and the pairwise SNP distances were 0 to 5 SNPs (median 2). Quantifying mutation frequencies is important for the longitudinal follow-up of epidemics of infections and outbreak management. Random pattern of pairwise SNP divergence between the strains isolated from single carriers suggested that the WGS of multiple colonies is necessary in this context. Over periods up to 3 years, maximum median core genome SNP counts and SNP divergence for the strains studied were 4 and 20 SNPs or lower. During artificial colonization, where median core genome SNP and pairwise SNP distance scores were 2, there is no early stage selection of different genotypes. Therefore, we suggest an epidemiological cut off value of 20 SNPs as a marker of S. aureus strain identity during studies on nasal colonization and also outbreaks of infection.
Highlights
Extensive use of antibiotics in the environment and the clinical domain contributes toward the emergence ofdrug resistant bacterial pathogens
The maximum number of pairwise single nucleotide polymorphism (SNP) differences calculated for the genomes of the isolates of carrier C ranged from 15 to 44 SNPs followed by 3 to 27 SNPs in strains from carrier D, 0 to 22 in strains from E, 7 to 20 in strains from B, 10 to 13 in strains from A and 0 to 9 SNPs in strains from F (Table 1)
The pattern of pairwise SNP differences is relatively random between the isolates from early and later stages of colonization
Summary
Extensive use of antibiotics in the environment and the clinical domain contributes toward the emergence of (multi-)drug resistant bacterial pathogens. This has become a global threat (Roca et al, 2015). S. aureus is a common opportunistic human pathogen identified most often on the nasal epithelium, About 30–50% of healthy individuals are persistently colonized (Wertheim et al, 2005). S. aureus causes a large variety of community as well as hospital-acquired infections. These include deep abscesses, endocarditis, osteomyelitis, pneumonia, and bloodstream infections (Foster and Höök, 1998; Rasigade and Vandenesch, 2014; Taylor and Unakal, 2018).
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