Mutations in NalC induce MexAB-OprM overexpression resulting in high level of aztreonam resistance in environmental isolates of Pseudomonas aeruginosa

Autor(es)

Braz, Vania S. ; Furlan, Joao Pedro R. ; Fernandes, Ana Flavia T. ; Stehling, Eliana G.

• Tipo de documento: Artigo Científico
• Fonte: FEMS Microbiology Letters; v. 363, n. 16 AUG 2016.
• Citações Web of Science: 14

Resumo

Pseudomonas aeruginosa is an opportunistic pathogen with high resistance to a wide variety of antimicrobials. The multidrug resistance pump MexAB-OprM promotes the efflux of various antibiotics, mostly when mutations accumulate in the transcriptional regulators MexR, NalC and NalD, thereby causing MexAB-OprM overexpression. In this work, a characterization of 50 P. aeruginosa isolates obtained from Brazilian agricultural soils to determine the reasons of their resistance to aztreonam was done. The majority of the isolates showed higher aztreonam resistance than wild-type strain by MIC method. DNA sequence analysis of mexR, nalC and nalD genes from 13 of these isolates showed the amino acid substitution in NalC for all tested isolates, just one mutation was detected in MexR and none in NalD. Furthermore, an increase in the level of mexA expression by real-time RT-PCR analysis in eight isolates harboring mutations in NalC was found. Although there was not a relationship between MIC of aztreonam and the level of mexA expression, on the other hand, the results presented here suggest that novel mutations in NalC, including Arg(97)-Gly and Ala(186)-Thr, are related to MexAB-OprM overexpression causing aztreonam resistance in P. aeruginosa environmental isolates. (AU)

• Processo FAPESP: 13/19401-5 - Pesquisa dos genes envolvidos na resistência aos carbapenêmicos e monobactâmicos em isolados ambientais de Pseudomonas aeruginosa
• Beneficiário: Eliana Guedes Stehling
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/02806-5 - Desenvolvimento de consórcios bacterianos para biodegradação da atrazina
• Beneficiário: Ana Flavia Tonelli Scaranello
• Modalidade de apoio: Bolsas no Brasil - Doutorado