The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin

Submitted by Janaína Nascimento ([email protected]) on 2019-11-07T13:30:51Z No. of bitstreams: 1 ve_Vianna_Júlia_etal_INI_2019.pdf: 709114 bytes, checksum: b1ed5809148e8413da3e93792838a4fa (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-11-08T12:27:37Z (GMT) No. of bitstreams: 1 ve_Vianna_Júlia_etal_INI_2019.pdf: 709114 bytes, checksum: b1ed5809148e8413da3e93792838a4fa (MD5)Made available in DSpace on 2019-11-08T12:27:38Z (GMT). No. of bitstreams: 1 ve_Vianna_Júlia_etal_INI_2019.pdf: 709114 bytes, checksum: b1ed5809148e8413da3e93792838a4fa (MD5) Previous issue date: 2019Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Global Health and Tropical Medicine. Lisboa, Portugal.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Global Health and Tropical Medicine. Lisboa, Portugal.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M.abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria