Unusual Inducible Cross Resistance to Macrolides, Lincosamides, and Streptogramins B by Methylase Production in Clinical Isolates ofStaphylococcus aureus

Abstract

Clinical strains of Staphylococcus aureus UCN7 and UCN8 were inducibly resistant to erythromycin, clindamycin, lincomycin, and quinupristin. This unusual inducible MLS(B) resistance was due to the presence of an erm(A) or an erm(B) gene, which both encode a ribosomal methylase, in S. aureus UCN8 and UCN7, respectively. The inducible cross resistance expressed by S. aureus UCN8 was associated with an 83-bp deletion in the attenuator of the erm(A) gene that removed the second of the two leader peptides and several inverted repeats. The presence of an inducible erm(B) gene in S. aureus UCN7 conferred a cross-resistance MLS(B) phenotype, similar to that usually observed in streptococci. Therefore, in S. aureus, besides the classical inducible MLS(B) phenotype characterized by inducible resistance to 14- to 15-membered ring macrolides, an additional type of inducible cross resistance to macrolides, lincosamides, and streptogramins B due to variants of erm(A) or erm(B) genes exist.

Modes and Modulations of Antibiotic Resistance Gene Expression

“…For instance, a clinical isolate of Enterococcus faecalis that contains an R7C mutation in the putative leader peptide of its erm(B) gene is more strongly induced by tylosin, a 16-membered macrolide, than by erythromycin (183). Similarly, a clinical isolate of S. aureus with an unusual inducible cross-resistance to erythromycin, clindamycin, lincomycin, and quinupristin had mutations in the attenuator of the erm(A) gene (52).…”

Programmed drug‐dependent ribosome stalling

“…The leader region of ermA contains two ORFs, ermAL1 and ermAL2 , which code for peptides that are 15 and 19 amino acids long respectively (Tables 1b and 2) (Murphy, 1985; Seppala et al ., 1998). The ErmAL2 sequence is almost identical to that of ErmCL (Table 2) which suggests that ermCL ‐like programmed ribosome stalling should be a part of the ermA induction mechanism (Clarebout et al ., 2001; Min et al ., 2008b). The sequence of the peptide encoded in the ermAL1 cistron is considerably different; nevertheless, drug‐dependent ribosome stalling can be detected at the ermAL1 ORF underscoring its role in regulation of ermA expression (H. Ramu, N. Vazquez‐Laslop and A. Mankin, in preparation).…”

Bactericidal activity of quinupristin-dalfopristin against strains of Staphylococcus aureus with the MLSB phenotype of resistance according to the erm gene type

“…Three other clinical isolates studied, S. aureus UCN7 and UCN11 with the erm(B) gene and UCN8 with the erm(A) gene displayed an unusual phenotype of inducible cross resistance to erythromycin, clindamycin and quinupristin. The genetic basis for inducible expression of MLS B resistance in S. aureus UCN7 and UCN8 has been previously studied [18]. Three S. aureus clinical isolates susceptible to MLS antibiotics and the clinical isolate, S. aureus UCN12, containing erm(C), with the classical inducible phenotype of resistance to erythromycin and susceptibility to clindamycin and quinupristin, were used as controls in killing experiments.…”