{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:04:12Z","timestamp":1780409052055,"version":"3.54.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The emergence of multidrug-resistant <jats:italic>Pseudomonas aeruginosa<\/jats:italic> isolates is a growing concern for public health, necessitating new therapeutic strategies. Gallium nitrate [Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub>], a medication for cancer-related hypercalcemia, has attracted great attention due to its ability to inhibit <jats:italic>P. aeruginosa<\/jats:italic> growth and biofilm formation by disrupting iron metabolism. However, the antibacterial efficacy of Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> is not always satisfactory. It is imperative to investigate the factors that affect the bactericidal effects of Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> and to identify new ways to enhance its efficacy. This study focused on the impact of pH on <jats:italic>P. aeruginosa<\/jats:italic> resistance to Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub>, along with the underlying mechanism. The results indicate that acidic conditions could increase the effectiveness of Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> against <jats:italic>P. aeruginosa<\/jats:italic> 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<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> against biofilm formation by <jats:italic>P. aeruginosa<\/jats:italic>, including a reference strain PA14 and several multidrug-resistant clinical isolates. Furthermore, we used an abscess mouse model to evaluate this combination <jats:italic>in vivo<\/jats:italic>; the results show that the combination of glutamic acid and Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> significantly improved <jats:italic>P. aeruginosa<\/jats:italic> clearance. Overall, the present study demonstrates that acidic conditions can increase the sensitivity of <jats:italic>P. aeruginosa<\/jats:italic> to Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub>. Combining glutamic acid and Ga(NO<jats:sub>3<\/jats:sub>)<jats:sub>3<\/jats:sub> is a potential strategy for the treatment of <jats:italic>P. aeruginosa<\/jats:italic> infections.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1464719","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T04:22:57Z","timestamp":1727151777000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["pH-mediated potentiation of gallium nitrate against Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"15","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxuan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1093\/cid\/ciac784","article-title":"Less is more? 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