Host specificity in the diversity and transfer of lsa resistance genes in group B Streptococcus

OBJECTIVES In group B Streptococcus (GBS), cross-resistance to lincosamides, streptogramin A and pleuromutilins (LSAP) is mediated by the acquisition of lsa genes. Here, we characterized the diversity, mobility and ecology of lsa genes in this species. METHODS lsa variants were systematically identified by BLAST searches in the genomes of 531 GBS strains from different hosts and geographical origins. The associated phenotypes were determined by a microdilution MIC method. Acquisition of resistance genes was deduced from comparative genomics and phylogeny. Their mobility was tested by conjugation experiments. RESULTS lsa(E) and three variants of lsa(C) were identified in GBS strains. Two lsa(C) variants had not been previously reported. All four variants conferred LSAP phenotypes. lsa(E) was located in a multiresistance gene cluster of a single human strain. This gene was transferred by a high-frequency recombination-type mechanism between GBS strains. Two lsa(C) variants are carried in six unrelated human strains by two similar elements specifically integrated in the oriT site of four different classes of integrative and conjugative elements (ICEs). Strikingly, the acquisition of the resistance gene always occurred by the integration of the element into a resident ICE. The third lsa(C) variant was located at the same site in the core genome of 11 genetically distant bovine strains and was likely propagated by horizontal transfer of the corresponding chromosomal region. CONCLUSIONS lsa genes in GBS show distinct host specificities and modes of transfer. In general, their dissemination is mediated by recombination rather than by the transfer of conjugative elements.