Identificaiton by genomic and genetic analysis of two new genes playing a key role in intermediate glycopeptide resistance in Staphylococcus aureus
| Autor: | Adriana Renzoni, Patrice Francois, Jacques Schrenzel, Pierre Vaudaux, Elzbieta Huggler, Christine Barras, Antoinette Monod, William L. Kelley, Daniel Pablo Lew, René Studer |
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| Rok vydání: | 2009 |
| Předmět: |
Staphylococcus aureus
Anti-Bacterial Agents/ pharmacology Genome Bacterial/ drug effects Microbial Sensitivity Tests Drug resistance Biology Staphylococcus aureus/ drug effects/ genetics/metabolism medicine.disease_cause Genetic analysis Mutation/drug effects Mechanisms of Resistance medicine Humans Pharmacology (medical) ORFS Glycopeptides/ genetics/metabolism Gene ddc:616 Pharmacology Genetics Comparative Genomic Hybridization Mutation Teicoplanin Glycopeptides Vancomycin Resistance Drug Resistance Microbial biochemical phenomena metabolism and nutrition Teicoplanin/pharmacology Glycopeptide Anti-Bacterial Agents Vancomycin Resistance/drug effects carbohydrates (lipids) Infectious Diseases Genome Bacterial medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, Vol. 53, No 3 (2009) pp. 903-911 |
| ISSN: | 0066-4804 |
| Popis: | Endogenous, low-level glycopeptide resistance in Staphylococcus aureus results from multifactorial genetic changes. Comparative genomic hybridization analysis revealed the specific deletion of a 1.8-kb segment encompassing two adjacent open reading frames (ORFs) of unknown function in a teicoplanin-susceptible revertant (strain 14-4rev) compared to the sequence of its isogenic, teicoplanin-resistant parental strain, strain 14-4. This provocative finding prompted us to perform a detailed genetic analysis of the contribution of this genomic segment to glycopeptide resistance. Despite repeated efforts in our laboratory, 14-4 and 14-4rev have proven refractory to most genetic manipulations. To circumvent this difficulty, we evaluated the contribution of both putative ORFs (designated teicoplanin resistance factors trfA and trfB ) on teicoplanin resistance in a different, genetically tractable background. Genetic analysis showed that single or double trfA and/or trfB mutations abolished teicoplanin resistance in two independent teicoplanin-resistant derivatives of NCTC8325 strain ISP794 generated by two-step passages with the drug. The frequency of teicoplanin-resistant mutants was markedly decreased by the absence of trfAB in the teicoplanin-susceptible ISP794 background. Nevertheless, a low rate of teicoplanin-resistant mutants was selected from ISP794 trfAB , thus indicating an additional contribution of trfAB -independent pathways in the emergence of low-level glycopeptide resistance. Further experiments performed with clinical glycopeptide-intermediate S. aureus isolate NRS3 indicated that the trfAB mutation could affect not only teicoplanin resistance but also vancomycin and oxacillin resistance. In conclusion, our study demonstrates the key role of two novel loci in endogenous, low-level glycopeptide resistance in S. aureus whose precise molecular functions warrant further investigation. |
| Databáze: | OpenAIRE |
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