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硝酸镓通过破坏多种铁依赖性代谢过程来抑制从血流感染中分离出的多重耐药鲍曼不动杆菌。

Gallium nitrate inhibits multidrug-resistant Acinetobacter baumannii isolated from bloodstream infection by disrupting multiple iron-dependent metabolic processes.

作者信息

Yao Zhuocheng, Yu Kaihang, Qian Changrui, Zhou Beibei, Lin Yishuai, Zhang Xiaodong, Zhang Ying, Zhou Tieli, Zeng Weiliang, Cao Jianming, Sun Yao

机构信息

Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.

Department of Pathology, the Second Affiliated Hospital, School of Medical, Zhejiang University, Hangzhou, Zhejiang Province, China.

出版信息

BMC Microbiol. 2025 Apr 14;25(1):216. doi: 10.1186/s12866-025-03950-4.

DOI:10.1186/s12866-025-03950-4
PMID:40229649
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11995626/
Abstract

BACKGROUND

Acinetobacter baumannii is a major pathogen in hospitals, causing a notable rise in bloodstream infections among inpatients. Its growing resistance to multiple drugs limits treatment options. This study aims to examine the antibacterial effects of gallium nitrate [Ga(NO)] against A. baumannii and elucidate the underlying molecular mechanism.

METHODS

40 strains of A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. The in vitro antibacterial activity of Ga(NO) was analyzed by micro-dilution method and time-kill assay. The influence of ferric chloride/hemin on the antibacterial efficacy of Ga(NO) was investigated. Transcriptome sequencing was performed to elucidate the antibacterial mechanism of Ga(NO). A mouse infection model was conducted to assess its in vivo performance.

RESULTS

Ga(NO) exhibited a potent antibacterial effect in RPMI 1640 medium containing 10% human serum, with MICs ranging from 0.06 μg/mL to 0.125 μg/mL. The antibacterial activity of Ga(NO) was found to be dose- and time- dependent. However, the antibacterial effect of Ga(NO) was partially compromised in the presence of exogenous ferric chloride/hemin. Transcriptomics analysis revealed that Ga(NO) exerted its antibacterial effect by up-regulating the expression of genes associated with siderophore biosynthesis and transport, while simultaneously disrupting multiple iron-dependent metabolic processes. Ga(NO) treatment significantly reduced bacterial load in vivo using a neutropenic mouse thigh infection model.

CONCLUSION

This study sheds light on the antibacterial mechanisms of Ga(NO) against A. baumannii, suggesting its potential as a promising antibacterial drug for treating bloodstream infections caused by multidrug-resistant A. baumannii.

摘要

背景

鲍曼不动杆菌是医院内的主要病原菌，导致住院患者血流感染显著增加。其对多种药物的耐药性不断增强，限制了治疗选择。本研究旨在考察硝酸镓[Ga(NO)]对鲍曼不动杆菌的抗菌作用，并阐明其潜在的分子机制。

方法

从血流感染中分离出40株具有不同抗菌药敏模式的鲍曼不动杆菌。采用微量稀释法和时间杀菌试验分析Ga(NO)的体外抗菌活性。研究了氯化铁/血红素对Ga(NO)抗菌效果的影响。进行转录组测序以阐明Ga(NO)的抗菌机制。建立小鼠感染模型以评估其体内性能。

结果

Ga(NO)在含10%人血清的RPMI 1640培养基中表现出强大的抗菌作用，MIC范围为0.06μg/mL至0.125μg/mL。发现Ga(NO)的抗菌活性具有剂量和时间依赖性。然而，在外源氯化铁/血红素存在的情况下，Ga(NO)的抗菌效果部分受损。转录组学分析表明，Ga(NO)通过上调与铁载体生物合成和转运相关的基因表达发挥抗菌作用，同时破坏多个铁依赖的代谢过程。使用中性粒细胞减少小鼠大腿感染模型，Ga(NO)治疗显著降低了体内细菌载量。

结论

本研究揭示了Ga(NO)对鲍曼不动杆菌的抗菌机制，表明其作为治疗多重耐药鲍曼不动杆菌引起的血流感染的有前景的抗菌药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/9c092af9b39d/12866_2025_3950_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/f600f99216de/12866_2025_3950_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/a0aa868a69da/12866_2025_3950_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/ac1393a37089/12866_2025_3950_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/9c092af9b39d/12866_2025_3950_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/f600f99216de/12866_2025_3950_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/a6aaf046493b/12866_2025_3950_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/878f90005706/12866_2025_3950_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/a0aa868a69da/12866_2025_3950_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/efdc23ca2da3/12866_2025_3950_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/091c3e415171/12866_2025_3950_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/ac1393a37089/12866_2025_3950_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6e/11995626/9c092af9b39d/12866_2025_3950_Fig8_HTML.jpg

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