Rescue of susceptibility to second-line drugs in resistant clinical isolates of Mycobacterium tuberculosis

Author:

Maringolo-Ribeiro Camila1ORCID,Grecco Júlia A1,Bellato Débora L1,Almeida Aryadne L2,Baldin Vanessa P2,Caleffi-Ferracioli Katiany R2ORCID,Pavan Fernando R1ORCID

Affiliation:

1. São Paulo State University (UNESP), School of Pharmaceutical Sciences, Tuberculosis Research Laboratory, Araraquara, São Paulo, Brazil

2. State University of Maringá (UEM), Department of Clinical Analysis & Biomedicine, Maringá, Paraná, Brazil

Abstract

Aim: Antibiotic resistance is one of the biggest threats to global health, and this study aimed better understand how the efflux pumps are related to this process in tuberculosis clinical isolates. Results: The combination of antibiotics plus efflux pumps (EP) inhibitors was able to restore the susceptibility of clinical isolates in 100% of aminoglycosides resistance and 33.3% of the fluoroquinolones resistance. The relative expression of EP genes in pre-extensively drug-resistant isolates showed an increase of up to 1000-times. Conclusion: The rescue of susceptibility in the presence of EP inhibitors, the increased of activity and expression of the EP genes alert that the inhibition of EP can reduce the selection of resistant strains and improve treatment.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado de São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Future Medicine Ltd

Subject

Microbiology (medical),Microbiology

Reference47 articles.

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4. World Health Organization. Meeting report of the WHO expert consultation on the definition of extensively drug-resistant tuberculosis (2020). www.who.int/publications/i/item/meeting-report-of-the-who-expert-consultation-on-the-definition-of-extensively-drug-resistant-tuberculosis

5. Recent updates on drug resistance in Mycobacterium tuberculosis

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