Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa

BackgroundPseudomonas aeruginosa is a common gram-negative opportunistic pathogen that is now commonly treated with carbapenems, such as Meropenem. However, the increasing rate of emergence of heteroresistant strains poses a therapeutic challenge. Therefore, we examined the antibacterial activity of...

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Main Authors: Zhihong Li, Tongtong Zhang, Ziqi Wang, Shuqiang Huang, Cuiyu Tan, Dan Wang, Xiaojun Yuan, Lingqing Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1523182/full
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author Zhihong Li
Tongtong Zhang
Ziqi Wang
Shuqiang Huang
Cuiyu Tan
Dan Wang
Xiaojun Yuan
Lingqing Xu
author_facet Zhihong Li
Tongtong Zhang
Ziqi Wang
Shuqiang Huang
Cuiyu Tan
Dan Wang
Xiaojun Yuan
Lingqing Xu
author_sort Zhihong Li
collection DOAJ
description BackgroundPseudomonas aeruginosa is a common gram-negative opportunistic pathogen that is now commonly treated with carbapenems, such as Meropenem. However, the increasing rate of emergence of heteroresistant strains poses a therapeutic challenge. Therefore, we examined the antibacterial activity of Sodium houttuyfonate (SH, a compound derived from Houttuynia cordata) in combination with Meropenem (MEM) against heteroresistant Pseudomonas aeruginosa and investigated the mechanism of Sodium houttuyfonate.MethodsHeteroresistant Pseudomonas aeruginosa was used as the experimental strain for the study and the combined action activity of the two drugs was inves-tigated by determining the Minimum Inhibitory Concentration (MIC), Fractional Inhibitory Concentration Index (FICI), and time killing curves. Also the effect of Sodium houttuyfonate on biofilm as well as bacterial swimming motility assay was investigated by crystal violet staining of bacterial biofilm, microanalysis of biofilm, bacterial swimming motility assay, quantitative real-time PCR (qRT-PCR) and population sensing related virulence factors.ResultsFor the screened experimental strains, the MIC of SH was 4,000 μg/ml; the FICI of both drugs on the four experimental strains was ≤0.5, which showed a synergistic effect. When SH ≥ 250 μg/ml, it was able to effectively inhibit bacterial biofilm formation as well as swimming ability compared with the blank control group. In the qRT-PCR experiment, the expression of biofilm formation-related genes (pslA, pelA, aglD, lasI, lasR, and rhlA) and swimming ability-related genes (fliC, pilZ, and pilA) were decreased in the SH-treated group, compared with the blank control group.ConclusionOur study demonstrated that Sodium houttuyfonate and Meropenem exhibited synergistic inhibition against heteroresistant Pseudomonas aeruginosa, and that Sodium houttuyfonate may achieve its inhibitory effect by inhibiting bacterial biofilm formation, inhibiting motility, and down-regulating related genes.
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series Frontiers in Microbiology
spelling doaj-art-078584a4d8bb4322978988923f95b4fa2025-08-20T03:02:06ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-03-011610.3389/fmicb.2025.15231821523182Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosaZhihong Li0Tongtong Zhang1Ziqi Wang2Shuqiang Huang3Cuiyu Tan4Dan Wang5Xiaojun Yuan6Lingqing Xu7Department of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Clinical Laboratory, The First People’s Hospital of Foshan, Foshan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaDepartment of Laboratory, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, ChinaBackgroundPseudomonas aeruginosa is a common gram-negative opportunistic pathogen that is now commonly treated with carbapenems, such as Meropenem. However, the increasing rate of emergence of heteroresistant strains poses a therapeutic challenge. Therefore, we examined the antibacterial activity of Sodium houttuyfonate (SH, a compound derived from Houttuynia cordata) in combination with Meropenem (MEM) against heteroresistant Pseudomonas aeruginosa and investigated the mechanism of Sodium houttuyfonate.MethodsHeteroresistant Pseudomonas aeruginosa was used as the experimental strain for the study and the combined action activity of the two drugs was inves-tigated by determining the Minimum Inhibitory Concentration (MIC), Fractional Inhibitory Concentration Index (FICI), and time killing curves. Also the effect of Sodium houttuyfonate on biofilm as well as bacterial swimming motility assay was investigated by crystal violet staining of bacterial biofilm, microanalysis of biofilm, bacterial swimming motility assay, quantitative real-time PCR (qRT-PCR) and population sensing related virulence factors.ResultsFor the screened experimental strains, the MIC of SH was 4,000 μg/ml; the FICI of both drugs on the four experimental strains was ≤0.5, which showed a synergistic effect. When SH ≥ 250 μg/ml, it was able to effectively inhibit bacterial biofilm formation as well as swimming ability compared with the blank control group. In the qRT-PCR experiment, the expression of biofilm formation-related genes (pslA, pelA, aglD, lasI, lasR, and rhlA) and swimming ability-related genes (fliC, pilZ, and pilA) were decreased in the SH-treated group, compared with the blank control group.ConclusionOur study demonstrated that Sodium houttuyfonate and Meropenem exhibited synergistic inhibition against heteroresistant Pseudomonas aeruginosa, and that Sodium houttuyfonate may achieve its inhibitory effect by inhibiting bacterial biofilm formation, inhibiting motility, and down-regulating related genes.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1523182/fullPseudomonas aeruginosaheteroresistant Pseudomonas aeruginosaMeropenemSodium houttuyfonatebiofilm
spellingShingle Zhihong Li
Tongtong Zhang
Ziqi Wang
Shuqiang Huang
Cuiyu Tan
Dan Wang
Xiaojun Yuan
Lingqing Xu
Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
Frontiers in Microbiology
Pseudomonas aeruginosa
heteroresistant Pseudomonas aeruginosa
Meropenem
Sodium houttuyfonate
biofilm
title Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
title_full Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
title_fullStr Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
title_full_unstemmed Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
title_short Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant Pseudomonas aeruginosa
title_sort antibacterial activity and mechanism of sodium houttuyfonate against heteroresistant pseudomonas aeruginosa
topic Pseudomonas aeruginosa
heteroresistant Pseudomonas aeruginosa
Meropenem
Sodium houttuyfonate
biofilm
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1523182/full
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