Cross-Resistance to Lincosamides, Streptogramins A, and Pleuromutilins Due to thelsa(C) Gene inStreptococcus agalactiaeUCN70

Abstract

ABSTRACTStreptococcus agalactiaeUCN70, isolated from a vaginal swab obtained in New Zealand, is resistant to lincosamides and streptogramins A (LSAphenotype) and also to tiamulin (a pleuromutilin). By whole-genome sequencing, we identified a 5,224-bp chromosomal extra-element that comprised a 1,479-bp open reading frame coding for an ABC protein (492 amino acids) 45% identical to Lsa(A), a protein related to intrinsic LSAresistance inEnterococcus faecalis. Expression of this novel gene, namedlsa(C), inS. agalactiaeBM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 μg/ml), clindamycin (0.03 to 2 μg/ml), dalfopristin (2 to >32 μg/ml), and tiamulin (0.12 to 32 μg/ml), whereas no change in MICs of erythromycin (0.06 μg/ml), azithromycin (0.03 μg/ml), spiramycin (0.25 μg/ml), telithromycin (0.03 μg/ml), and quinupristin (8 μg/ml) was observed. The phenotype was renamed the LSAP phenotype on the basis of cross-resistance tolincosamides,streptograminsA, andpleuromutilins. This gene was also identified in similar genetic environments in 17 otherS. agalactiaeclinical isolates from New Zealand exhibiting the same LSAP phenotype, whereas it was absent in susceptibleS. agalactiaestrains. Interestingly, this extra-element was bracketed by a 7-bp duplication of a target site (ATTAGAA), suggesting that this structure was likely a mobile genetic element. In conclusion, we identified a novel gene,lsa(C), responsible for the acquired LSAP resistance phenotype inS. agalactiae. Dissection of the biochemical basis of resistance, as well as demonstration ofin vitromobilization oflsa(C), remains to be performed.