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Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii.
Boonyalai, Nonlawat; Peerapongpaisarn, Dutsadee; Thamnurak, Chatchadaporn; Oransathid, Wilawan; Wongpatcharamongkol, Nantanat; Oransathid, Wirote; Lurchachaiwong, Woradee; Griesenbeck, John S; Waters, Norman C; Demons, Samandra T; Ruamsap, Nattaya; Vesely, Brian A.
Afiliación
  • Boonyalai N; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Peerapongpaisarn D; Biological Chemistry and Drug Discovery, Wellcome Centre for Anti-Infectives Research, University of Dundee, Dundee, UK.
  • Thamnurak C; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Oransathid W; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Wongpatcharamongkol N; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Oransathid W; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Lurchachaiwong W; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Griesenbeck JS; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Waters NC; Division of Global Health Protection, Thailand MoPH-US CDC Collaboration, Nonthaburi, Thailand.
  • Demons ST; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Ruamsap N; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
  • Vesely BA; Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
Sci Rep ; 14(1): 21709, 2024 09 17.
Article en En | MEDLINE | ID: mdl-39289446
ABSTRACT
Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC50s ≤ 48 µM for A. baumannii QS17-1084 and IC50s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Acinetobacter / Pruebas de Sensibilidad Microbiana / Farmacorresistencia Bacteriana Múltiple / Acinetobacter baumannii / Antibacterianos Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Acinetobacter / Pruebas de Sensibilidad Microbiana / Farmacorresistencia Bacteriana Múltiple / Acinetobacter baumannii / Antibacterianos Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido