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Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii

Antibiotic-resistant Acinetobacter baumannii infections among patients in hospital settings are rising at an alarming rate. The World Health Organization has designated carbapenem-resistant A. baumannii as a priority pathogen for drug discovery. Based on the open drug discovery approach, we screened...

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Detalles Bibliográficos
Autores principales: Upmanyu, Kirti, Rizwanul Haq, Qazi Mohd., Singh, Ruchi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375957/
https://www.ncbi.nlm.nih.gov/pubmed/37508252
http://dx.doi.org/10.3390/antibiotics12071155
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author Upmanyu, Kirti
Rizwanul Haq, Qazi Mohd.
Singh, Ruchi
author_facet Upmanyu, Kirti
Rizwanul Haq, Qazi Mohd.
Singh, Ruchi
author_sort Upmanyu, Kirti
collection PubMed
description Antibiotic-resistant Acinetobacter baumannii infections among patients in hospital settings are rising at an alarming rate. The World Health Organization has designated carbapenem-resistant A. baumannii as a priority pathogen for drug discovery. Based on the open drug discovery approach, we screened 400 compounds provided as a Pandemic Response Box by MMV and DNDi to identify compounds with antibacterial and antibiofilm activity against two A. baumannii reference strains using a highly robust resazurin assay. In vitro screening identified thirty compounds with MIC ≤ 50μM having growth inhibitory properties against the planktonic state. Five compounds, with MMV IDs MMV396785, MMV1578568, MMV1578574, MMV1578564, and MMV1579850, were able to reduce metabolically active cells in the biofilm state. Of these five compounds, MMV396785 showed potential antibacterial and antibiofilm activity with MIC, MBIC, and MBEC of 3.125 μM, 12.5, and 25–100 µM against tested A. baumannii strains, respectively, showing biofilm formation inhibition by 93% and eradication of pre-formed biofilms by 60–77.4%. In addition, MMV396785 showed a drastic reduction in the surface area and thickness of biofilms. Further investigations at the molecular level by qRT-PCR revealed the downregulation of biofilm-associated genes when exposed to 50 µM MMV396785 in all tested strains. This study identified the novel compound MMV396785 as showing potential in vitro antibacterial and antibiofilm efficacy against A. baumannii.
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spelling pubmed-103759572023-07-29 Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii Upmanyu, Kirti Rizwanul Haq, Qazi Mohd. Singh, Ruchi Antibiotics (Basel) Article Antibiotic-resistant Acinetobacter baumannii infections among patients in hospital settings are rising at an alarming rate. The World Health Organization has designated carbapenem-resistant A. baumannii as a priority pathogen for drug discovery. Based on the open drug discovery approach, we screened 400 compounds provided as a Pandemic Response Box by MMV and DNDi to identify compounds with antibacterial and antibiofilm activity against two A. baumannii reference strains using a highly robust resazurin assay. In vitro screening identified thirty compounds with MIC ≤ 50μM having growth inhibitory properties against the planktonic state. Five compounds, with MMV IDs MMV396785, MMV1578568, MMV1578574, MMV1578564, and MMV1579850, were able to reduce metabolically active cells in the biofilm state. Of these five compounds, MMV396785 showed potential antibacterial and antibiofilm activity with MIC, MBIC, and MBEC of 3.125 μM, 12.5, and 25–100 µM against tested A. baumannii strains, respectively, showing biofilm formation inhibition by 93% and eradication of pre-formed biofilms by 60–77.4%. In addition, MMV396785 showed a drastic reduction in the surface area and thickness of biofilms. Further investigations at the molecular level by qRT-PCR revealed the downregulation of biofilm-associated genes when exposed to 50 µM MMV396785 in all tested strains. This study identified the novel compound MMV396785 as showing potential in vitro antibacterial and antibiofilm efficacy against A. baumannii. MDPI 2023-07-06 /pmc/articles/PMC10375957/ /pubmed/37508252 http://dx.doi.org/10.3390/antibiotics12071155 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Upmanyu, Kirti
Rizwanul Haq, Qazi Mohd.
Singh, Ruchi
Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title_full Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title_fullStr Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title_full_unstemmed Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title_short Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii
title_sort antibacterial and antibiofilm properties of the alexidine dihydrochloride (mmv396785) against acinetobacter baumannii
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10375957/
https://www.ncbi.nlm.nih.gov/pubmed/37508252
http://dx.doi.org/10.3390/antibiotics12071155
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