Nontuberculous mycobacteria (NTM) comprise several ubiquitous, environmentally localized bacteria that may be responsible for serious human diseases. NTM-associated pulmonary infections largely affect individuals with underlying respiratory disease or chronic disease and immunosuppressed patients. Mycobacterium simiae and M. abscessus are two NTMs responsible for lung disease in immunocompetent and immunocompromised individuals. In this study, two NTM strains were isolated from two patients admitted to an Italian hospital and were identified as M. simiae and M. abscessus. The two NTMs were tested for drug susceptibility against different antibiotics. To restore drug susceptibility, a new series of 2-aryl-3-phenoxymethyl-quinoxaline derivatives (QXs) was designed, synthesized, and investigated as efflux pump inhibitors (EPIs) against two clinical isolates of the above-cited NTMs, evaluating how EPIs can influence the drug minimal inhibitory concentration values and, therefore, the activity. The different\ resistance levels tracked in the clinical strains were reduced by EPIs, and in several cases, the susceptibility was completely restored. QXs also resulted as potential chemical probes to be used in drug susceptibility tests to identify the resistance origin when detected.

Quinoxaline-based efflux pump inhibitors restore drug susceptibility in drug-resistant nontuberculous mycobacteria / Corona, Paola; Ibba, Roberta; Piras, Sandra; Molicotti, Paola; Bua, Alessandra; Carta, Antonio. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - 355:8(2022), pp. 1-8. [10.1002/ardp.202100492]

Quinoxaline-based efflux pump inhibitors restore drug susceptibility in drug-resistant nontuberculous mycobacteria

Corona, Paola
Membro del Collaboration Group
;
Ibba, Roberta
Membro del Collaboration Group
;
Piras, Sandra
Membro del Collaboration Group
;
Molicotti, Paola
Membro del Collaboration Group
;
Bua, Alessandra
Membro del Collaboration Group
;
Carta, Antonio
Membro del Collaboration Group
2022-01-01

Abstract

Nontuberculous mycobacteria (NTM) comprise several ubiquitous, environmentally localized bacteria that may be responsible for serious human diseases. NTM-associated pulmonary infections largely affect individuals with underlying respiratory disease or chronic disease and immunosuppressed patients. Mycobacterium simiae and M. abscessus are two NTMs responsible for lung disease in immunocompetent and immunocompromised individuals. In this study, two NTM strains were isolated from two patients admitted to an Italian hospital and were identified as M. simiae and M. abscessus. The two NTMs were tested for drug susceptibility against different antibiotics. To restore drug susceptibility, a new series of 2-aryl-3-phenoxymethyl-quinoxaline derivatives (QXs) was designed, synthesized, and investigated as efflux pump inhibitors (EPIs) against two clinical isolates of the above-cited NTMs, evaluating how EPIs can influence the drug minimal inhibitory concentration values and, therefore, the activity. The different\ resistance levels tracked in the clinical strains were reduced by EPIs, and in several cases, the susceptibility was completely restored. QXs also resulted as potential chemical probes to be used in drug susceptibility tests to identify the resistance origin when detected.
2022
Quinoxaline-based efflux pump inhibitors restore drug susceptibility in drug-resistant nontuberculous mycobacteria / Corona, Paola; Ibba, Roberta; Piras, Sandra; Molicotti, Paola; Bua, Alessandra; Carta, Antonio. - In: ARCHIV DER PHARMAZIE. - ISSN 0365-6233. - 355:8(2022), pp. 1-8. [10.1002/ardp.202100492]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/301893
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