10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus

Antimicrobial resistance (AMR) is a global concern that undermines microbial disease treatment and prevention. WHO and World Bank's EcoAMR report predicts that AMR could cause 39 million deaths and $3.4 trillion in annual GDP losses by the year 2050. This is particularly critical with S. aureus...

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Main Authors: Hiren Dodia, Suvendu Ojha, Puja Chatterjee, Tushar Kant Beuria
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Biofilm
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590207525000553
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author Hiren Dodia
Suvendu Ojha
Puja Chatterjee
Tushar Kant Beuria
author_facet Hiren Dodia
Suvendu Ojha
Puja Chatterjee
Tushar Kant Beuria
author_sort Hiren Dodia
collection DOAJ
description Antimicrobial resistance (AMR) is a global concern that undermines microbial disease treatment and prevention. WHO and World Bank's EcoAMR report predicts that AMR could cause 39 million deaths and $3.4 trillion in annual GDP losses by the year 2050. This is particularly critical with S. aureus, a cause of diverse infections like skin abscesses and pneumonia, where antibiotic resistance increases mortality and hinders treatment. Biofilms are one of the major causes of multi-drug resistance in S. aureus, and their inhibition can restore antibiotic sensitivity. In this study, through screening of the LOPAC drug library, we identified several compounds that exhibit biofilm inhibitory properties against multi-drug-resistant S. aureus without affecting its growth. The compound 10058-F4 was found to have the strongest anti-biofilm activity (>70 % inhibition) with minimal antibacterial effects (MIC 256 μg/mL); however, it showed no inhibitory effects on pre-existing biofilm. Further, the 10058-F4 treatment suppressed the expression of sarA, the biofilm master regulator, along with biofilm genes, such as icaA, fnb, nuc, and sspA. Additionally, the results showed that 10058-F4 synergistically enhanced the antibacterial activity of norfloxacin and tetracycline, indicating its potential use as an adjunct to the existing antibiotic treatments. While these findings suggest the potential of 10058-F4 for clinical use, further investigations are necessary to elucidate its mechanism of action and optimize its application in combination therapies.
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spelling doaj-art-be4bd5f596b14f3ba6cd7e2f5fb1fd7e2025-07-21T04:10:04ZengElsevierBiofilm2590-20752025-12-011010030710058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureusHiren Dodia0Suvendu Ojha1Puja Chatterjee2Tushar Kant Beuria3Department of Infectious Disease Biology, Institute of Life Sciences, NALCO Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India; Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad Rd, Faridabad, Haryana, 121001, IndiaDepartment of Infectious Disease Biology, Institute of Life Sciences, NALCO Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India; Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad Rd, Faridabad, Haryana, 121001, IndiaDepartment of Infectious Disease Biology, Institute of Life Sciences, NALCO Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India; Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad Rd, Faridabad, Haryana, 121001, IndiaDepartment of Infectious Disease Biology, Institute of Life Sciences, NALCO Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023, India; Corresponding author.Antimicrobial resistance (AMR) is a global concern that undermines microbial disease treatment and prevention. WHO and World Bank's EcoAMR report predicts that AMR could cause 39 million deaths and $3.4 trillion in annual GDP losses by the year 2050. This is particularly critical with S. aureus, a cause of diverse infections like skin abscesses and pneumonia, where antibiotic resistance increases mortality and hinders treatment. Biofilms are one of the major causes of multi-drug resistance in S. aureus, and their inhibition can restore antibiotic sensitivity. In this study, through screening of the LOPAC drug library, we identified several compounds that exhibit biofilm inhibitory properties against multi-drug-resistant S. aureus without affecting its growth. The compound 10058-F4 was found to have the strongest anti-biofilm activity (>70 % inhibition) with minimal antibacterial effects (MIC 256 μg/mL); however, it showed no inhibitory effects on pre-existing biofilm. Further, the 10058-F4 treatment suppressed the expression of sarA, the biofilm master regulator, along with biofilm genes, such as icaA, fnb, nuc, and sspA. Additionally, the results showed that 10058-F4 synergistically enhanced the antibacterial activity of norfloxacin and tetracycline, indicating its potential use as an adjunct to the existing antibiotic treatments. While these findings suggest the potential of 10058-F4 for clinical use, further investigations are necessary to elucidate its mechanism of action and optimize its application in combination therapies.http://www.sciencedirect.com/science/article/pii/S2590207525000553Staphylococcus aureus10058-F4LOPAC drug libraryBiofilm inhibitorDrug repurposingAntimicrobial resistance (AMR)
spellingShingle Hiren Dodia
Suvendu Ojha
Puja Chatterjee
Tushar Kant Beuria
10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
Biofilm
Staphylococcus aureus
10058-F4
LOPAC drug library
Biofilm inhibitor
Drug repurposing
Antimicrobial resistance (AMR)
title 10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
title_full 10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
title_fullStr 10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
title_full_unstemmed 10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
title_short 10058-F4 Mediated inhibition of the biofilm formation in multidrug-resistant Staphylococcus aureus
title_sort 10058 f4 mediated inhibition of the biofilm formation in multidrug resistant staphylococcus aureus
topic Staphylococcus aureus
10058-F4
LOPAC drug library
Biofilm inhibitor
Drug repurposing
Antimicrobial resistance (AMR)
url http://www.sciencedirect.com/science/article/pii/S2590207525000553
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AT pujachatterjee 10058f4mediatedinhibitionofthebiofilmformationinmultidrugresistantstaphylococcusaureus
AT tusharkantbeuria 10058f4mediatedinhibitionofthebiofilmformationinmultidrugresistantstaphylococcusaureus