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H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization

文献类型：期刊论文

作者Sun, Jiekai1; Wang, Xu1; Gao, Ye1; Li, Shuangyu1; Hu, Ziwei1; Huang, Yan1; Fan, Baoqiang2; Wang, Xia1; Liu, Miao1; Qiao, Chunhua1
刊名NATURE COMMUNICATIONS
出版日期2024-10-31
卷号15期号:1页码:17
DOI10.1038/s41467-024-53764-7
通讯作者Zhang, Wei(zhang_wei@sdu.edu.cn) ; Wang, Yipeng(yipengwang@suda.edu.cn) ; Ji, Xingyue(jixy@suda.edu.cn)
英文摘要Bacteria-derived H2S plays multifunctional protective roles against antibiotics insult, and the H2S biogenesis pathway is emerging as a viable target for the antibacterial adjuvant design. However, the development of a pan-inhibitor against H2S-synthesizing enzymes is challenging and underdeveloped. Herein, we propose an alternative strategy to downregulate the H2S levels in H2S-producing bacteria, which depletes the bacteria-derived H2S chemically by H2S scavengers without acting on the synthesizing enzymes. After the screening of chemically diversified scaffolds and a structural optimization campaign, a potent and specific H2S scavenger is successfully identified, which displays efficient H2S depletion in several H2S-producing bacteria, potentiates both bactericidal agents and photodynamic therapy, enhances the bacterial clearance of macrophages and polymorphonuclear neutrophils, disrupts the formation of bacterial biofilm and increases the sensitivity of bacterial persister cells to antibiotics. Most importantly, such an H2S scavenger exhibits sensitizing effects with gentamicin in Pseudomonas aeruginosa -infected pneumonia and skin wound female mouse models. In aggregate, our results not only provide an effective strategy to deplete bacteria-derived H2S and establish the H2S biogenesis pathway as a viable target for persisters and drug-resistant bacteria, but also deliver a promising antibacterial adjuvant for potential clinical translation. Bacteria-derived H2S functions as a universal defense against antibiotics challenge. Here, Ji et al developed a broad-spectrum H2S scavenger that efficiently removes endogenous H2S in several bacteria, disrupts biofilm formation and sensitizes persister cells to antibiotic-mediated killing in vitro and in vivo.
WOS关键词HYDROGEN-SULFIDE ; ANTIBIOTIC-RESISTANCE ; PERSISTER CELLS ; TOLERANCE ; PROBES ; INHIBITORS
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001346309700016
资助机构National Natural Science Foundation of China (National Science Foundation of China) ; National Natural Science Foundation of China ; Jiangsu Specially-Appointed Professor Program ; Key Research & Development Plan in Social Development of Jiangsu Province ; Suzhou Agricultural Science and Technology Innovation Project ; Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD)
源URL[http://ir.yic.ac.cn/handle/133337/37874]  
专题中国科学院烟台海岸带研究所
通讯作者Zhang, Wei; Wang, Yipeng; Ji, Xingyue
作者单位1.Soochow Univ, Coll Pharmaceut Sci, Jiangsu Prov Engn Res Ctr Precis Diag & Therapeut, Suzhou, Jiangsu, Peoples R China
2.Shandong Univ, State Key Lab Microbial Technol, Qingdao, Shandong, Peoples R China
3.Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai, Peoples R China
推荐引用方式
GB/T 7714		 Sun, Jiekai,Wang, Xu,Gao, Ye,et al. H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization[J]. NATURE COMMUNICATIONS,2024,15(1):17.
APA Sun, Jiekai.,Wang, Xu.,Gao, Ye.,Li, Shuangyu.,Hu, Ziwei.,...&Ji, Xingyue.(2024).H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization.NATURE COMMUNICATIONS,15(1),17.
MLA Sun, Jiekai,et al."H2S scavenger as a broad-spectrum strategy to deplete bacteria-derived H2S for antibacterial sensitization".NATURE COMMUNICATIONS 15.1(2024):17.

入库方式： OAI收割

来源：烟台海岸带研究所

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