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

Made available in DSpace on 2022-04-28T18:45:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-23 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Sao Paulo State University Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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. Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, TB Res Lab, Araraquara, SP, Brazil State Univ Maringa UEM, Dept Clin Anal & Biomed, Maringa, Parana, Brazil Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, TB Res Lab, Araraquara, SP, Brazil FAPESP: FAPESP 2018/02344-2 FAPESP: 2018/12135-1 FAPESP: 2020/13497-4 CAPES: 001