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Characterization of sal(A), a novel gene responsible for lincosamide and streptogramin A resistance in Staphylococcus sciuri.

ABSTRACT: Natural resistance to lincosamides and streptogramins A (LSA), which is a species characteristic of Bacillus subtilis and Enterococcus faecalis, has never been documented in the Staphylococcus genus. We investigate here the molecular basis of the LSA phenotype exhibited by seven reference strains of Staphylococcus sciuri, including the type strains of the three described subspecies. By whole-genome sequencing of strain ATCC 29059, we identified a candidate gene that encodes an ATP-binding cassette protein similar to the Lsa and VmlR resistance determinants. Isolation and reverse transcription-quantitative PCR (qRT-PCR) expression studies confirmed that Sal(A) can confer a moderate resistance to lincosamides (8 times the MIC of lincomycin) and a high-level resistance to streptogramins A (64 times the MIC of pristinamycin II). The chromosomal location of sal(A) between two housekeeping genes of the staphylococcal core genome supports the gene's ancient origins and thus innate resistance to these antimicrobials within S. sciuri subspecies.

SUBMITTER: Hot C

PROVIDER: S-EPMC4068490 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Characterization of sal(A), a novel gene responsible for lincosamide and streptogramin A resistance in Staphylococcus sciuri.

Hot Chloé C Berthet Nicolas N Chesneau Olivier O

Antimicrobial agents and chemotherapy 20140331 6

Natural resistance to lincosamides and streptogramins A (LSA), which is a species characteristic of Bacillus subtilis and Enterococcus faecalis, has never been documented in the Staphylococcus genus. We investigate here the molecular basis of the LSA phenotype exhibited by seven reference strains of Staphylococcus sciuri, including the type strains of the three described subspecies. By whole-genome sequencing of strain ATCC 29059, we identified a candidate gene that encodes an ATP-binding casset ...[more]

PMID: 24687494

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Project description:BackgroundSolithromycin, the fourth generation of ketolides, has been demonstrated potent antibacterial effect against commonly-isolated gram-positive strains. However, Staphylococcus aureus (S. aureus) strains with a higher solithromycin MIC have already been emerged, the mechanism of which is unknown.MethodsAntimicrobial susceptibility test was performed on 266 strains of S. aureus. The antibiotic resistance phenotype of erm-positive strain was determined by D-zone test. Spontaneous mutation frequency analysis was performed to compare the risk levels for solithromycin resistance among different strains. Efflux pumps and mutational analysis of ribosomal fragments as well as erm(B) gene domains were detected. Quantitative reverse transcription polymerase chain reaction was conducted to compare the transcriptional expression of the erm gene between the constitutive macrolide-lincosamide-streptogramin B (cMLSB)- and inducible MLSB (iMLSB)-phenotypes.ResultsIn the erm-positive S. aureus strains, the minimum inhibitory concentration (MIC)50/90 of solithromycin (2/> 16 mg/L) was significantly higher than that in the erm-negative strains (0.125/0.25 mg/L). Of note, the MIC50 value of the strains with iMLSB (0.25 mg/L) was significantly lower than that of the strains with cMLSB (4 mg/L). A comparison among strains demonstrated that the median mutational frequency in isolates with cMLSB (> 1.2 × 10- 4) was approximately > 57-fold and > 3333-fold higher than that in iMLSB strains (2.1 × 10- 6) and in erythromycin-sensitive strains (3.6 × 10- 8), respectively. The differential antibiotic in vitro activity against strains between cMLSB and iMLSB could not be explained by efflux pump carriers or genetic mutations in the test genes. The expression of the erm genes in strains with cMLSB did not differ from that in strains with iMLSB.ConclusionsThe reduced susceptibility to solithromycin by S. aureus was associated with the cMLSB resistance phenotype mediated by erm.

Dataset Information

Characterization of sal(A), a novel gene responsible for lincosamide and streptogramin A resistance in Staphylococcus sciuri.

Publications

Characterization of sal(A), a novel gene responsible for lincosamide and streptogramin A resistance in Staphylococcus sciuri.

Similar Datasets

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