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Antibiotics 2018, 7(2), 36; https://doi.org/10.3390/antibiotics7020036

Specificity of Induction of Glycopeptide Antibiotic Resistance in the Producing Actinomycetes

1
Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy
2
The Protein Factory Research Center, Politecnico di Milano and University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy
*
Author to whom correspondence should be addressed.
Received: 28 February 2018 / Revised: 19 April 2018 / Accepted: 20 April 2018 / Published: 25 April 2018
(This article belongs to the Special Issue Actinomycetes: The Antibiotics Producers)
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Abstract

Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by Gram-positive pathogens. It is widely believed that glycopeptide-resistance determinants (van genes) are ultimately derived from the producing actinomycetes. We hereby investigated the relationship between the antimicrobial activity of vancomycin and teicoplanins and their differential ability to induce van gene expression in Actinoplanes teichomyceticus—the producer of teicoplanin—and Nonomuraea gerenzanensis—the producer of the teicoplanin-like A40926. As a control, we used the well-characterized resistance model Streptomyces coelicolor. The enzyme activities of a cytoplasmic-soluble d,d-dipeptidase and of a membrane-associated d,d-carboxypeptidase (corresponding to VanX and VanY respectively) involved in resistant cell wall remodeling were measured in the actinomycetes grown in the presence or absence of subinhibitory concentrations of vancomycin, teicoplanin, and A40926. Results indicated that actinomycetes possess diverse self-resistance mechanisms, and that each of them responds differently to glycopeptide induction. Gene swapping among teicoplanins-producing actinomycetes indicated that cross-talking is possible and provides useful information for predicting the evolution of future resistance gene combinations emerging in pathogens. View Full-Text
Keywords: actinomycetes; glycopeptide antibiotics; teicoplanin; A40926; van resistance genes actinomycetes; glycopeptide antibiotics; teicoplanin; A40926; van resistance genes
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Binda, E.; Cappelletti, P.; Marinelli, F.; Marcone, G.L. Specificity of Induction of Glycopeptide Antibiotic Resistance in the Producing Actinomycetes. Antibiotics 2018, 7, 36.

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