2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa

Siderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting s...

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Main Authors: Lujun Yin, Wang Shen, Jun-Sheng Liu, Ai-Qun Jia
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.955952/full
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author Lujun Yin
Wang Shen
Jun-Sheng Liu
Ai-Qun Jia
Ai-Qun Jia
author_facet Lujun Yin
Wang Shen
Jun-Sheng Liu
Ai-Qun Jia
Ai-Qun Jia
author_sort Lujun Yin
collection DOAJ
description Siderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting siderophore production. 2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN), one siderophore inhibitor of Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), was obtained by using the Chromeazurol S (CAS) method. We found that HMMN inhibited siderophore production and influenced the biological effects of QS regulation, including biofilm formation and pyocyanin production. HMMN (150 μg/ml) inhibited the siderophore production of P. aeruginosa PAO1 by 69.37%. In addition, HMMN could inhibit pyocyanin production and biofilm formation and erase the formed biofilm of P. aeruginosa PAO1. HMMN (150 μg/ml) inhibited the biofilm formation of P. aeruginosa PAO1 by 28.24%. The erasure rate of the formed biofilm reached 17.03%. Furthermore, HMMN (150 μg/ml) inhibited P. aeruginosa PAO1 pyocyanin production by 36.06%. Meanwhile, positive-control hordenine (500.0 μg/ml) reduced the biofilm formation and pyocyanin production of P. aeruginosa PAO1 by 14.42% and 34.35%, respectively. The erasure rate of hordenine to the formed biofilm is 11.05% at 500 μg/ml. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that HMMN downregulates not only siderophore-related genes but also QS-related genes, as well as hordenine. These results suggest that a siderophore inhibitor could be used as a QS inhibitor to occlude the QS system and reduce virulence.
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spelling doaj.art-d53d75f7796d4c57aa02213d445b14ca2022-12-22T03:12:16ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.9559529559522-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosaLujun Yin0Wang Shen1Jun-Sheng Liu2Ai-Qun Jia3Ai-Qun Jia4School of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, ChinaSchool of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, ChinaSchool of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, ChinaSchool of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, ChinaOne Health Institute, Hainan University, Haikou, ChinaSiderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting siderophore production. 2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN), one siderophore inhibitor of Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), was obtained by using the Chromeazurol S (CAS) method. We found that HMMN inhibited siderophore production and influenced the biological effects of QS regulation, including biofilm formation and pyocyanin production. HMMN (150 μg/ml) inhibited the siderophore production of P. aeruginosa PAO1 by 69.37%. In addition, HMMN could inhibit pyocyanin production and biofilm formation and erase the formed biofilm of P. aeruginosa PAO1. HMMN (150 μg/ml) inhibited the biofilm formation of P. aeruginosa PAO1 by 28.24%. The erasure rate of the formed biofilm reached 17.03%. Furthermore, HMMN (150 μg/ml) inhibited P. aeruginosa PAO1 pyocyanin production by 36.06%. Meanwhile, positive-control hordenine (500.0 μg/ml) reduced the biofilm formation and pyocyanin production of P. aeruginosa PAO1 by 14.42% and 34.35%, respectively. The erasure rate of hordenine to the formed biofilm is 11.05% at 500 μg/ml. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that HMMN downregulates not only siderophore-related genes but also QS-related genes, as well as hordenine. These results suggest that a siderophore inhibitor could be used as a QS inhibitor to occlude the QS system and reduce virulence.https://www.frontiersin.org/articles/10.3389/fcimb.2022.955952/full2-hydroxymethyl-1-methyl-5-nitroimidazolesiderophore inhibitorquorum sensingvirulence factorbiofilmPseudomonas aeruginosa
spellingShingle Lujun Yin
Wang Shen
Jun-Sheng Liu
Ai-Qun Jia
Ai-Qun Jia
2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
Frontiers in Cellular and Infection Microbiology
2-hydroxymethyl-1-methyl-5-nitroimidazole
siderophore inhibitor
quorum sensing
virulence factor
biofilm
Pseudomonas aeruginosa
title 2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
title_full 2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
title_fullStr 2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
title_full_unstemmed 2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
title_short 2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
title_sort 2 hydroxymethyl 1 methyl 5 nitroimidazole one siderophore inhibitor occludes quorum sensing in pseudomonas aeruginosa
topic 2-hydroxymethyl-1-methyl-5-nitroimidazole
siderophore inhibitor
quorum sensing
virulence factor
biofilm
Pseudomonas aeruginosa
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.955952/full
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