An operon encoding enzymes for synthesis of a putative extracellular carbohydrate attenuates acquired vancomycin resistance in Streptomyces coelicolor
| Autor: | Robert Howlett, Nicholas Read, Margaret C. M. Smith |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic Operon Mannose Streptomyces coelicolor Microbiology Phosphates 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Vancomycin Drug Resistance Multiple Bacterial Glycosyltransferase medicine 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology ATP synthase 030306 microbiology Teicoplanin Extracellular Polymeric Substance Matrix Glycosyltransferases Vancomycin Resistance Gene Expression Regulation Bacterial biology.organism_classification Anti-Bacterial Agents Enzyme chemistry Multigene Family Mutation biology.protein Bacteria medicine.drug Protein Binding Transcription Factors |
| Zdroj: | Microbiology (Reading, England). 165(2) |
| ISSN: | 1465-2080 |
| Popis: | Actinomycete bacteria use polyprenol phosphate mannose as a lipid-linked sugar donor for extra-cytoplasmic glycosyl transferases that transfer mannose to cell envelope polymers, including glycoproteins and glycolipids. Strains of Streptomyces coelicolor with mutations in the gene ppm1, encoding polyprenol phosphate mannose synthase, and in pmt, encoding a protein O-mannosyltransferase, are resistant to phage ϕC31 and have greatly increased susceptibility to some antibiotics, including vancomycin. In this work, second-site suppressors of the vancomycin susceptibility were isolated. The suppressor strains fell into two groups. Group 1 strains had increased resistance to vancomycin, teicoplanin and β-lactams, and had mutations in the two-component sensor regulator system encoded by vanSR, leading to upegulation of the vanSRJKHAX cluster. Group 2 strains only had increased resistance to vancomycin and these mostly had mutations in sco2592 or sco2593, genes that are derepressed in the presence of phosphate and are likely to be required for the synthesis of a phosphate-containing extracellular polymer. In some suppressor strains the increased resistance was only observed in media with limited phosphate (mimicking the phenotype of wild-type S. coelicolor ), but two strains, DT3017_R21 (ppm1-vanR -) and DT3017_R15 (ppm1- sco2593 -), retained resistance on media with high phosphate content. These results support the view that vancomycin resistance in S. coelicolor is a trade-off between mechanisms that confer resistance and at least one that interferes with resistance mediated through the sco2594-sco2593-sco2592 operon. |
| Databáze: | OpenAIRE |
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