Your browser doesn't support javascript.
loading
AdeIJK Pump-Specific Inhibitors Effective against Multidrug Resistant Acinetobacter baumannii.
Tambat, Rushikesh; Kinthada, Rama Kumar; Saral Sariyer, Aysegul; Leus, Inga V; Sariyer, Emrah; D'Cunha, Napoleon; Zhou, Hinman; Leask, Makaila; Walker, John K; Zgurskaya, Helen I.
Afiliación
  • Tambat R; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
  • Kinthada RK; School of Medicine, Saint Louis University, St. Louis, Missouri 63110, United States.
  • Saral Sariyer A; Department of Nutrition and Dietetics, Faculty of Health Sciences, Artvin Coruh University, 08000 Artvin, Turkey.
  • Leus IV; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.
  • Sariyer E; Department of Nutrition and Dietetics, Faculty of Health Sciences, Artvin Coruh University, 08000 Artvin, Turkey.
  • D'Cunha N; Vocational School of Health Services, Medical Laboratory Techniques, Artvin Coruh University, 08000 Artvin, Turkey.
  • Zhou H; School of Medicine, Saint Louis University, St. Louis, Missouri 63110, United States.
  • Leask M; School of Medicine, Saint Louis University, St. Louis, Missouri 63110, United States.
  • Walker JK; School of Medicine, Saint Louis University, St. Louis, Missouri 63110, United States.
  • Zgurskaya HI; School of Medicine, Saint Louis University, St. Louis, Missouri 63110, United States.
ACS Infect Dis ; 10(6): 2239-2249, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38787939
ABSTRACT
Multidrug-resistant Acinetobacter baumannii is a serious threat pathogen rapidly spreading in clinics and causing a range of complicated human infections. The major contributor to A. baumannii antibiotic resistance is the overproduction of AdeIJK and AdeABC multidrug efflux pumps of the resistance-nodulation-division (RND) superfamily of proteins. The dominant role of efflux in antibiotic resistance and the relatively high permeability of the A. baumannii outer membrane to amphiphilic compounds make this pathogen a promising target for the discovery of clinically relevant efflux pump inhibitors. In this study, we identified 4,6-diaminoquoniline analogs with inhibitory activities against A. baumannii AdeIJK efflux pump and followed up on these compounds with a focused synthetic program to improve the target specificity and to reduce cytotoxicity. We identified several candidates that potentiate antibacterial activities of antibiotics erythromycin, tetracycline, and novobiocin not only in the laboratory antibiotic susceptible strain A. baumannii ATCC17978 but also in multidrug-resistant clinical isolates AB5075 and AYE. The best analogs potentiated the activities of antibiotics in low micromolar concentrations, did not have antibacterial activities on their own, inhibited AdeIJK-mediated efflux of its fluorescent substrate ethidium ion, and had low cytotoxicity in A549 human lung epithelial cells.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Infecciones por Acinetobacter / Farmacorresistencia Bacteriana Múltiple / Acinetobacter baumannii / Antibacterianos Límite: Humans Idioma: En Revista: ACS Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Infecciones por Acinetobacter / Farmacorresistencia Bacteriana Múltiple / Acinetobacter baumannii / Antibacterianos Límite: Humans Idioma: En Revista: ACS Infect Dis Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos