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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Resistance in In Vitro Selected Tigecycline-Resistant Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Is Driven by Mutations in mepR and mepA Genes

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Author(s):
Gebieluca Dabul, Andrei Nicoli [1] ; Avaca-Crusca, Juliana Sposto [1] ; Van Tyne, Daria [2, 3] ; Gilmore, Michael S. [2, 3] ; Baratella Cunha Camargo, Ilana Lopes [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Sao Carlos Inst Phys, Dept Phys & Interdisciplinary Sci, POB 369, BR-13560970 Sao Carlos, SP - Brazil
[2] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA - USA
[3] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA - USA
Total Affiliations: 3
Document type: Journal article
Source: MICROBIAL DRUG RESISTANCE; v. 24, n. 5, p. 519-526, JUN 2018.
Web of Science Citations: 9
Abstract

A tigecycline-susceptible (TGC-S) Sequence Type (ST) 5 clinical methicillin-resistant Staphylococcus aureus (MRSA) strain was cultured in escalating levels of tigecycline, yielding mutants eightfold more resistant. Their genomes were sequenced to identify genetic alterations, resulting in resistance. Alterations in rpsJ, commonly related to tigecycline resistance, were also investigated. Tigecycline resistance was mediated by loss-of-function mutations in the transcriptional repressor mepR, resulting in derepression of the efflux pump mepA. Increased levels of resistance were obtained by successive mutations in mepA itself. No alterations in RpsJ were observed in selected strains, but we observed a K57M substitution, previously correlated with resistance, among TGC-S clinical strains. Thus, the pathway to tigecycline resistance in CC5 MRSA in vitro appears to be derepression of mep operon as the result of mepR loss-of-function mutation, followed by alterations in MepA efflux pump. This shows that other evolutionary pathways, besides mutation of rpsJ, are available for evolving tigecycline resistance in CC5 MRSA. (AU)

FAPESP's process: 10/02619-0 - Molecular epidemiological study of Brazilian strains of Methicillin-resistant Staphylococcus aureus (MRSA) isolated in Brazil and study of the response regulator protein GraR
Grantee:Ilana Lopes Baratella da Cunha Camargo
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/24952-0 - Patterns of emergence of multidrug resistant enterococci and staphylococci in Brazil and search for new drugs
Grantee:Andrei Nicoli Gebieluca Dabul Dias de Sousa
Support type: Scholarships in Brazil - Post-Doctorate