Development of small molecules that work cooperatively with ciprofloxacin to clear salmonella biofilms in a chronic gallbladder carriage model.
Development of small molecules that work cooperatively with ciprofloxacin to clear salmonella biofilms in a chronic gallbladder carriage model.
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DOI：
10.1016/j.ejmech.2022.114203
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发表时间：
2022-03-15
影响因子：
6.7
通讯作者：
Melander C
中科院分区：
文献类型：
--
作者：
Woolard KJ;Sandala JL;Melander RJ;Gunn JS;Melander C
肠道沙门氏菌血清型每年引起数百万例感染，导致伤寒或沙门氏菌病。在引起伤寒的血清型中，肠道沙门氏菌伤寒亚种可以在急性感染患者的胆囊中的胆结石上形成生物膜，导致细菌的慢性携带。这些生物膜对抗生素介导的根除是不利的，导致细菌的慢性粪便脱落，这导致进一步的疾病传播。在此，我们报告了一个55个成员的小分子文库的合成和抗生物膜活性，该文库基于先前鉴定的既抑制又破坏S.伤寒和沙门氏菌。鼠伤寒（S.伤寒）生物膜。铅化合物抑制S.在亚微摩尔浓度下体外鼠伤寒生物膜形成，并以比母体化合物高五倍的效力分散生物膜。三种最有前途的化合物在慢性沙门氏菌携带的小鼠模型中表现出与环丙沙星的协同作用。这项工作进一步发展了有效的抗生物膜剂作为一个有前途的治疗途径，根除伤寒沙门氏菌。
Salmonella enterica serovars cause millions of infections each year that result either in typhoid fever or salmonellosis. Among those serovars that cause typhoid fever, Salmonella enterica subspecies Typhi can form biofilms on gallstones in the gallbladders of acutely-infected patients, leading to chronic carriage of the bacterium. These biofilms are recalcitrant to antibiotic-mediated eradication, leading to chronic fecal shedding of the bacteria, which results in further disease transmission. Herein, we report the synthesis and anti-biofilm activity of a 55-member library of small molecules based upon a previously identified hit that both inhibits and disrupts S. Typhi and S. Typhimurium (a nontyphoidal model serovar for S. Typhi) biofilms. Lead compounds inhibit S. Typhimurium biofilm formation in vitro at sub-micromolar concentrations, and disperse biofilms with five-fold greater potentency than the parent compound. Three of the most promising compounds demonstrated synergy with ciprofloxacin in a murine model of chronic Salmonella carriage. This work furthers the development of effective anti-biofilm agents as a promising therapeutic avenue for the eradication of typhoidal Salmonella.
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一种新的小分子可在体外和体内抑制变形链球菌生物膜。
影响因子：
4
作者：
Pan W;Fan M;Wu H;Melander C;Liu C
通讯作者：
Liu C
DOI：
10.1136/bmj.b1865
发表时间：
2009-06-03
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Thaver D;Zaidi AK;Critchley J;Azmatullah A;Madni SA;Bhutta ZA
通讯作者：
Bhutta ZA
影响因子：
56.3
作者：
Stanaway, Jeffrey D.;Reiner, Robert C.;Hay, Simon I.
通讯作者：
Hay, Simon I.
DOI：
10.1073/pnas.1000862107
发表时间：
2010-03-02
影响因子：
11.1
作者：
Crawford, Robert W.;Rosales-Reyes, Roberto;Gunn, John S.
通讯作者：
Gunn, John S.
影响因子：
15.9
作者：
Gunn, John S.;Marshall, Joanna M.;Baker, Stephen;Dongol, Sabina;Charles, Richelle C.;Ryan, Edward T.
通讯作者：
Ryan, Edward T.