Genomic diversity of Staphylococcus aureus in singly-colonized nasal carriers and the implications for detecting recent transmission

We used Illumina sequencing to investigate the genetic variation within 131 S. aureus genomes sampled from 13 asymptomatic, singly colonized nasal carriers, including five carriers of methicillin resistant S. aureus (MRSA). We discovered 162 single nucleotide polymorphisms and 22 short insertions/deletions among ten hosts, revealing that microvariation is a common feature of nasal carriage. Structural variation in the S. aureus genome associated with insertion or excision of mobile elements was also apparent. The fitness landscape during colonization was dominated by purifying selection and reduced diversity was associated with MRSA carriage or the recent use of antibiotics. Total diversity and variation in allele frequencies across individuals were consistent with longitudinal fluctuation in intra-host population size. Based on our observations, we developed a simple model for the likelihood of recent transmission given the degree of genomic divergence, inferring that one pair of MRSA carriers in the study may have been related by as few as three transmission events.