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The novel macrolide-Lincosamide-Streptogramin B resistance gene erm(44) is associated with a prophage in Staphylococcus xylosus.

ABSTRACT: A novel erythromycin ribosome methylase gene, erm(44), that confers resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics was identified by whole-genome sequencing of the chromosome of Staphylococcus xylosus isolated from bovine mastitis milk. The erm(44) gene is preceded by a regulatory sequence that encodes two leader peptides responsible for the inducible expression of the methylase gene, as demonstrated by cloning in Staphylococcus aureus. The erm(44) gene is located on a 53-kb putative prophage designated ?JW4341-pro. The 56 predicted open reading frames of ?JW4341-pro are structurally organized into the five functional modules found in members of the family Siphoviridae. ?JW4341-pro is site-specifically integrated into the S. xylosus chromosome, where it is flanked by two perfect 19-bp direct repeats, and exhibits the ability to circularize. The presence of erm(44) in three additional S. xylosus strains suggests that this putative prophage has the potential to disseminate MLSB resistance.

SUBMITTER: Wipf JR

PROVIDER: S-EPMC4187952 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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The novel macrolide-Lincosamide-Streptogramin B resistance gene erm(44) is associated with a prophage in Staphylococcus xylosus.

Wipf Juliette R K JR Schwendener Sybille S Perreten Vincent V

Antimicrobial agents and chemotherapy 20140804 10

A novel erythromycin ribosome methylase gene, erm(44), that confers resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics was identified by whole-genome sequencing of the chromosome of Staphylococcus xylosus isolated from bovine mastitis milk. The erm(44) gene is preceded by a regulatory sequence that encodes two leader peptides responsible for the inducible expression of the methylase gene, as demonstrated by cloning in Staphylococcus aureus. The erm(44) gene is located o ...[more]

PMID: 25092709

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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

The novel macrolide-Lincosamide-Streptogramin B resistance gene erm(44) is associated with a prophage in Staphylococcus xylosus.

Publications

The novel macrolide-Lincosamide-Streptogramin B resistance gene erm(44) is associated with a prophage in Staphylococcus xylosus.

Similar Datasets

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