Chang Liu, Chenxuan Cui, Xiaoxin Tan, Junjie Miao, Wei Wang, Han Ren, Hua Wu, Cuiying Zheng, Huan Ren, Weijun Kang
{"title":"pH-mediated potentiation of gallium nitrate against <i>Pseudomonas aeruginosa</i>.","authors":"Chang Liu, Chenxuan Cui, Xiaoxin Tan, Junjie Miao, Wei Wang, Han Ren, Hua Wu, Cuiying Zheng, Huan Ren, Weijun Kang","doi":"10.3389/fmicb.2024.1464719","DOIUrl":null,"url":null,"abstract":"<p><p>The emergence of multidrug-resistant <i>Pseudomonas aeruginosa</i> isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO<sub>3</sub>)<sub>3</sub>], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit <i>P. aeruginosa</i> growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO<sub>3</sub>)<sub>3</sub> is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO<sub>3</sub>)<sub>3</sub> and to identify new ways to enhance its efficacy. This study focused on the impact of pH on <i>P. aeruginosa</i> resistance to Ga(NO<sub>3</sub>)<sub>3</sub>, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO<sub>3</sub>)<sub>3</sub> against <i>P. aeruginosa</i> by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO<sub>3</sub>)<sub>3</sub> against biofilm formation by <i>P. aeruginosa</i>, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination <i>in vivo</i>; the results show that the combination of glutamic acid and Ga(NO<sub>3</sub>)<sub>3</sub> significantly improved <i>P. aeruginosa</i> clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of <i>P. aeruginosa</i> to Ga(NO<sub>3</sub>)<sub>3</sub>. Combining glutamic acid and Ga(NO<sub>3</sub>)<sub>3</sub> is a potential strategy for the treatment of <i>P. aeruginosa</i> infections.</p>","PeriodicalId":12466,"journal":{"name":"Frontiers in Microbiology","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458400/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmicb.2024.1464719","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The emergence of multidrug-resistant Pseudomonas aeruginosa isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO3)3], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit P. aeruginosa growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO3)3 is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO3)3 and to identify new ways to enhance its efficacy. This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO3)3, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO3)3 against P. aeruginosa by promoting the production of pyochelin and gallium uptake. Subsequently, using glutamic acid, a clinically compatible acidic amino acid, the pH was significantly lowered and enhanced the bactericidal and inhibitory efficacy of Ga(NO3)3 against biofilm formation by P. aeruginosa, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination in vivo; the results show that the combination of glutamic acid and Ga(NO3)3 significantly improved P. aeruginosa clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of P. aeruginosa to Ga(NO3)3. Combining glutamic acid and Ga(NO3)3 is a potential strategy for the treatment of P. aeruginosa infections.
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.