<i>Staphylococcus haemolyticus</i> is a reservoir of antibiotic resistance genes in the preterm infant gut

<i>Staphylococcus haemolyticus</i> is an important cause of sepsis in preterm infants, with gut colonization being recognized as a risk factor for infection. To better understand the diversity of <i>S. haemolyticus</i> among preterm infants, we generated genome sequences of <i>S. haemolyticus</i> strains (<i>n</i> = 140) from 44 stool samples of 22 preterm infants from four hospitals in England. Core genome phylogenetic analyses, incorporating 126 publicly available <i>S. haemolyticus</i> genome sequences, showed that 85/140 (60.1%) of the isolates, from three different hospitals, formed a clonal group with 78/85 (91.7%) strains having Multi-Locus Sequence Type (ST) 49. Antibiotic resistance genes were prevalent in the genomes. There was a strong association between the presence of <i>mecA</i> and phenotypic resistance to oxacillin, and the <i>aacA-aphD</i> gene and phenotypic resistance to gentamicin. While <i>mecA</i> was near-ubiquitous, none of the strains from the preterm infant cohort had a complete Staphylococcal Cassette Chromosome <i>mec</i> (SCC<i>mec</i>) element. The <i>aacA-aphD</i> gene was associated with the transposon Tn<i>4001</i> in multiple chromosomal and plasmid contexts. Our data suggest the existence of a distinct sub-population of <i>S. haemolyticus</i> that has adapted to colonize the gut of preterm infants, and widespread horizontal gene transfer and recombination among this frequent colonizer of the preterm infant gut.