Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii

ABSTRACT Acinetobacter baumannii is a critical priority gram-negative bacterial species featured with multidrug resistance and biofilm formation. This study screened 46 indole derivative agents for their antimicrobial activities against clinical isolates of extensively drug-resistant A. baumannii (X...

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Main Authors: Junwei Li, Lulin Xie, Fei Lin, Baodong Ling
Format: Article
Language:English
Published: American Society for Microbiology 2025-05-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.03388-24
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author Junwei Li
Lulin Xie
Fei Lin
Baodong Ling
author_facet Junwei Li
Lulin Xie
Fei Lin
Baodong Ling
author_sort Junwei Li
collection DOAJ
description ABSTRACT Acinetobacter baumannii is a critical priority gram-negative bacterial species featured with multidrug resistance and biofilm formation. This study screened 46 indole derivative agents for their antimicrobial activities against clinical isolates of extensively drug-resistant A. baumannii (XDRAB) with various degrees of biofilm production. Three selected indole agents—5-iodoindole, 3-methylindole, and 7-hydroxyindole—were revealed to display potent antimicrobial and antibiofilm activity, including synergistic interplay with anti-A. baumannii antimicrobial drugs against XDRAB. Sub-inhibitory concentrations of these agents (particularly 7-hydroxyindole at 1/64 of MIC) not only inhibited XDRAB biofilm formation but also eradicated the mature biofilm. The survival rate of XDRAB-infected Galleria mellonella was improved with the treatment of 7-hydroxyindole. Mechanistically, 7-hydroxyindole was found to reduce the expression of quorum sensing/biofilm-implicated genes abaI and abaR. Together, the findings highlight the potential of indole derivatives against A. baumannii infections.IMPORTANCEExtensively drug-resistant Acinetobacter baumannii (XDRAB) isolates pose a major public health threat to antimicrobial therapy and are highly prevalent in hospital settings. This study identified and characterized indole derivative agents for their antimicrobial and antibiofilm activities against XDRAB. Sub-inhibitory indole agents such as 7-hydroxyindole can both inhibit XDRAB biofilm formation and eradicate the mature biofilm. Indole agents warrant further investigation against hard-to-treat antimicrobial-resistant pathogens.
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spelling doaj-art-ad443b5e80fa40b8b9dccfe173a1be7c2025-08-20T03:52:32ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-05-0113510.1128/spectrum.03388-24Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumanniiJunwei Li0Lulin Xie1Fei Lin2Baodong Ling3Key Laboratory of Structure-Specific Small Molecule Drugs at Chengdu Medical College of Sichuan Province, School of Pharmacy, Chengdu Medical College, Chengdu, ChinaKey Laboratory of Structure-Specific Small Molecule Drugs at Chengdu Medical College of Sichuan Province, School of Pharmacy, Chengdu Medical College, Chengdu, ChinaDepartment of Pharmacy, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, ChinaKey Laboratory of Structure-Specific Small Molecule Drugs at Chengdu Medical College of Sichuan Province, School of Pharmacy, Chengdu Medical College, Chengdu, ChinaABSTRACT Acinetobacter baumannii is a critical priority gram-negative bacterial species featured with multidrug resistance and biofilm formation. This study screened 46 indole derivative agents for their antimicrobial activities against clinical isolates of extensively drug-resistant A. baumannii (XDRAB) with various degrees of biofilm production. Three selected indole agents—5-iodoindole, 3-methylindole, and 7-hydroxyindole—were revealed to display potent antimicrobial and antibiofilm activity, including synergistic interplay with anti-A. baumannii antimicrobial drugs against XDRAB. Sub-inhibitory concentrations of these agents (particularly 7-hydroxyindole at 1/64 of MIC) not only inhibited XDRAB biofilm formation but also eradicated the mature biofilm. The survival rate of XDRAB-infected Galleria mellonella was improved with the treatment of 7-hydroxyindole. Mechanistically, 7-hydroxyindole was found to reduce the expression of quorum sensing/biofilm-implicated genes abaI and abaR. Together, the findings highlight the potential of indole derivatives against A. baumannii infections.IMPORTANCEExtensively drug-resistant Acinetobacter baumannii (XDRAB) isolates pose a major public health threat to antimicrobial therapy and are highly prevalent in hospital settings. This study identified and characterized indole derivative agents for their antimicrobial and antibiofilm activities against XDRAB. Sub-inhibitory indole agents such as 7-hydroxyindole can both inhibit XDRAB biofilm formation and eradicate the mature biofilm. Indole agents warrant further investigation against hard-to-treat antimicrobial-resistant pathogens.https://journals.asm.org/doi/10.1128/spectrum.03388-24Acinetobacter baumanniiextensive drug resistancebiofilmindoles
spellingShingle Junwei Li
Lulin Xie
Fei Lin
Baodong Ling
Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
Microbiology Spectrum
Acinetobacter baumannii
extensive drug resistance
biofilm
indoles
title Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
title_full Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
title_fullStr Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
title_full_unstemmed Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
title_short Indole derivatives display antimicrobial and antibiofilm effects against extensively drug-resistant Acinetobacter baumannii
title_sort indole derivatives display antimicrobial and antibiofilm effects against extensively drug resistant acinetobacter baumannii
topic Acinetobacter baumannii
extensive drug resistance
biofilm
indoles
url https://journals.asm.org/doi/10.1128/spectrum.03388-24
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AT lulinxie indolederivativesdisplayantimicrobialandantibiofilmeffectsagainstextensivelydrugresistantacinetobacterbaumannii
AT feilin indolederivativesdisplayantimicrobialandantibiofilmeffectsagainstextensivelydrugresistantacinetobacterbaumannii
AT baodongling indolederivativesdisplayantimicrobialandantibiofilmeffectsagainstextensivelydrugresistantacinetobacterbaumannii