Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70.
Streptococcus agalactiae UCN70, isolated from a vaginal swab obtained in New Zealand, is resistant to lincosamides and streptogramins A (LS(A) phenotype) 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 LS(A) resistance in Enterococcus faecalis. Expression of this novel gene, named lsa(C), in S. agalactiae BM132 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 LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins. This gene was also identified in similar genetic environments in 17 other S. agalactiae clinical isolates from New Zealand exhibiting the same LS(A)P phenotype, whereas it was absent in susceptible S. agalactiae strains. 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 LS(A)P resistance phenotype in S. agalactiae. Dissection of the biochemical basis of resistance, as well as demonstration of in vitro mobilization of lsa(C), remains to be performed.
Service de Microbiologie and EA 2128, Relations Hôte et Microorganismes des Epithéliums, Hôpital Côte de Nacre, Université de Caen Basse-Normandie, Caen, France.
Brigitte
B
Malbruny
Anja M
AM
Werno
David R
DR
Murdoch
Roland
R
Leclercq
Vincent
V
Cattoir
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D055231:Lincosamides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D011083:Polycyclic Compounds; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013292:Streptococcus agalactiae / Q000187:drug effects* / Q000235:genetics; D025361:Streptogramins / Q000494:pharmacology*; D000097567:Pleuromutilins
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004224:Diterpenes; D055231:Lincosamides; D011083:Polycyclic Compounds; D025361:Streptogramins; D000097567:Pleuromutilins
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