Apramycin Overcomes the Inherent Lack of Antimicrobial Bactericidal Activity in Mycobacterium abscessus.
Antimicrob Agents Chemother
; 66(2): e0151021, 2022 02 15.
Article
em En
| MEDLINE
| ID: mdl-34930031
ABSTRACT
Antibiotic therapy of infections caused by the emerging pathogen Mycobacterium abscessus is challenging due to the organism's inherent resistance to clinically available antimicrobials. The low bactericidal potency of currently available treatment regimens is of concern and testifies to the poor therapeutic outcomes for pulmonary M. abscessus infections. Mechanistically, we demonstrate here that the acetyltransferase Eis2 is responsible for the lack of bactericidal activity of amikacin, the standard aminoglycoside used in combination treatment. In contrast, the aminoglycoside apramycin, with a distinct structure, is not modified by any of the pathogen's innate aminoglycoside resistance mechanisms and is not affected by the multidrug resistance regulator WhiB7. As a consequence, apramycin uniquely shows potent bactericidal activity against M. abscessus. This favorable feature of apramycin is reflected in a mouse model of pulmonary M. abscessus infection, which demonstrates superior activity, compared with amikacin. These findings encourage the development of apramycin for the treatment of M. abscessus infections and suggest that M. abscessus eradication in pulmonary disease may be within therapeutic reach.
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Base de dados:
MEDLINE
Assunto principal:
Mycobacterium abscessus
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Infecções por Mycobacterium não Tuberculosas
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Nebramicina
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article