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Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is a nosocomial pathogen associated with urinary tract infections and expresses several virulence factors that cause recurring infections and cystitis of the bladder, which can lead to pyelonephritis. UPEC uses different types of extracellular appendages like fi...

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Autores principales: Boya, Bharath Reddy, Lee, Jin-Hyung, Lee, Jintae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244173/
https://www.ncbi.nlm.nih.gov/pubmed/35783430
http://dx.doi.org/10.3389/fmicb.2022.872943
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author Boya, Bharath Reddy
Lee, Jin-Hyung
Lee, Jintae
author_facet Boya, Bharath Reddy
Lee, Jin-Hyung
Lee, Jintae
author_sort Boya, Bharath Reddy
collection PubMed
description Uropathogenic Escherichia coli (UPEC) is a nosocomial pathogen associated with urinary tract infections and expresses several virulence factors that cause recurring infections and cystitis of the bladder, which can lead to pyelonephritis. UPEC uses different types of extracellular appendages like fimbriae and pili that aid colonization and adherence to bladder epithelium and can form persistent biofilm-like bacterial communities that aid its survival after the deployment of host immune responses. We investigated the antibiofilm, antimicrobial, and antivirulence properties of three indole derivatives namely, 4-chloroindole, 5-chloroindole, and 5-chloro 2-methyl indole. All the three chloroindoles had MICs of 75 μg/ml and inhibited biofilm formation by an average of 67% at 20 μg/ml. In addition, they inhibited swarming and swimming motilities, which are essential for dissemination from bacterial communities and colonization, reduced cell surface hydrophobicity, and inhibited indole production and curli formation. Gene expression analysis showed all three chloroindoles significantly downregulated the expressions of virulence genes associated with adhesion, stress regulation, and toxin production. A 3D-QSAR analysis revealed substitutions at the fourth and fifth positions of the indole moiety favored antimicrobial activity. Furthermore, these chloroindoles potently inhibited biofilm formation in other nosocomial pathogens and polymicrobial consortia.
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spelling pubmed-92441732022-07-01 Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli Boya, Bharath Reddy Lee, Jin-Hyung Lee, Jintae Front Microbiol Microbiology Uropathogenic Escherichia coli (UPEC) is a nosocomial pathogen associated with urinary tract infections and expresses several virulence factors that cause recurring infections and cystitis of the bladder, which can lead to pyelonephritis. UPEC uses different types of extracellular appendages like fimbriae and pili that aid colonization and adherence to bladder epithelium and can form persistent biofilm-like bacterial communities that aid its survival after the deployment of host immune responses. We investigated the antibiofilm, antimicrobial, and antivirulence properties of three indole derivatives namely, 4-chloroindole, 5-chloroindole, and 5-chloro 2-methyl indole. All the three chloroindoles had MICs of 75 μg/ml and inhibited biofilm formation by an average of 67% at 20 μg/ml. In addition, they inhibited swarming and swimming motilities, which are essential for dissemination from bacterial communities and colonization, reduced cell surface hydrophobicity, and inhibited indole production and curli formation. Gene expression analysis showed all three chloroindoles significantly downregulated the expressions of virulence genes associated with adhesion, stress regulation, and toxin production. A 3D-QSAR analysis revealed substitutions at the fourth and fifth positions of the indole moiety favored antimicrobial activity. Furthermore, these chloroindoles potently inhibited biofilm formation in other nosocomial pathogens and polymicrobial consortia. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9244173/ /pubmed/35783430 http://dx.doi.org/10.3389/fmicb.2022.872943 Text en Copyright © 2022 Boya, Lee and Lee. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Boya, Bharath Reddy
Lee, Jin-Hyung
Lee, Jintae
Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title_full Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title_fullStr Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title_full_unstemmed Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title_short Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli
title_sort antibiofilm and antimicrobial activities of chloroindoles against uropathogenic escherichia coli
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244173/
https://www.ncbi.nlm.nih.gov/pubmed/35783430
http://dx.doi.org/10.3389/fmicb.2022.872943
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