{"title":"Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistant <i>Pseudomonas aeruginosa</i>.","authors":"Zhihong Li, Tongtong Zhang, Ziqi Wang, Shuqiang Huang, Cuiyu Tan, Dan Wang, Xiaojun Yuan, Lingqing Xu","doi":"10.3389/fmicb.2025.1523182","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong><i>Pseudomonas aeruginosa</i> 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 <i>Houttuynia cordata</i>) in combination with Meropenem (MEM) against heteroresistant <i>Pseudomonas aeruginosa</i> and investigated the mechanism of Sodium houttuyfonate.</p><p><strong>Methods: </strong>Heteroresistant <i>Pseudomonas aeruginosa</i> 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.</p><p><strong>Results: </strong>For 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 (<i>pslA</i>, <i>pelA</i>, <i>aglD</i>, <i>lasI</i>, <i>lasR</i>, and <i>rhlA</i>) and swimming ability-related genes (<i>fliC</i>, <i>pilZ</i>, and <i>pilA</i>) were decreased in the SH-treated group, compared with the blank control group.</p><p><strong>Conclusion: </strong>Our study demonstrated that Sodium houttuyfonate and Meropenem exhibited synergistic inhibition against heteroresistant <i>Pseudomonas aeruginosa</i>, and that Sodium houttuyfonate may achieve its inhibitory effect by inhibiting bacterial biofilm formation, inhibiting motility, and down-regulating related genes.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":"16 ","pages":"1523182"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922930/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmicb.2025.1523182","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Pseudomonas 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.
Methods: Heteroresistant 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.
Results: For 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.
Conclusion: Our 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.
期刊介绍：
Frontiers in Microbiology is a leading journal in its field, publishing rigorously peer-reviewed research across the entire spectrum of microbiology. Field Chief Editor Martin G. Klotz at Washington State University is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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