A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage.
A dual-therapy approach for the treatment of biofilm-mediated Salmonella gallbladder carriage.
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DOI：
10.1371/journal.ppat.1009192
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发表时间：
2020-12
期刊：
影响因子：
6.7
通讯作者：
Gunn JS
中科院分区：
文献类型：
--
作者：
Sandala JL;Eichar BW;Kuo LG;Hahn MM;Basak AK;Huggins WM;Woolard K;Melander C;Gunn JS
伤寒沙门氏菌的无症状携带继续促进伤寒的传播，每年造成1 400万新感染和136 000人死亡。无症状的慢性S。伤寒是通过在胆结石上形成生物膜来促进的，生物膜保护细菌免受环境的侵害和免疫系统的清除。在这里，我们确定了两种独特的小分子，能够抑制沙门氏菌生物膜生长和破坏预先形成的生物膜结构，而不影响细菌的活力。在慢性胆囊沙门氏菌携带的小鼠模型中，用任一种化合物治疗使胆囊中的细菌负荷降低1-2个对数，导致细菌传播至外周器官，这与死亡率增加相关。任一化合物与环丙沙星的共同给药不仅使化合物在胆囊中的功效进一步增强1-1.5 log，总共减少3-4.5 log，而且还防止细菌传播到外周器官。这些数据表明，靶向生物膜和增殖细胞群体的双重治疗方法可以进一步发展为生物膜介导的慢性S。伤寒感染。伤寒是一种由伤寒沙门氏菌引起的传染病。伤寒），一种每年导致多达1400万新感染和136,000人死亡的细菌。无症状的慢性S.伤寒在伤寒的传播中起着重要作用，因为它们间歇性地散发细菌，并能在不知不觉中感染周围的人。在这里，我们表征了靶向生物膜形成的新型化合物，生物膜形成是S.伤寒建立和维持胆囊中的慢性携带，希望它们最终可以与传统抗生素结合使用，以预防和/或治疗慢性感染，比单独使用抗生素更有效。
Asymptomatic carriage of Salmonella Typhi continues to facilitate the transmission of typhoid fever, resulting in 14 million new infections and 136,000 fatalities each year. Asymptomatic chronic carriage of S. Typhi is facilitated by the formation of biofilms on gallstones that protect the bacteria from environmental insults and immune system clearance. Here, we identified two unique small molecules capable of both inhibiting Salmonella biofilm growth and disrupting pre-formed biofilm structures without affecting bacterial viability. In a mouse model of chronic gallbladder Salmonella carriage, treatment with either compound reduced bacterial burden in the gallbladder by 1–2 logs resulting in bacterial dissemination to peripheral organs that was associated with increased mortality. Co-administration of either compound with ciprofloxacin not only enhanced compound efficacy in the gallbladder by a further 1–1.5 logs for a total of 3–4.5 log reduction, but also prevented bacterial dissemination to peripheral organs. These data suggest a dual-therapy approach targeting both biofilm and planktonic populations can be further developed as a safe and efficient treatment of biofilm-mediated chronic S. Typhi infections. Typhoid fever is an infectious disease caused by Salmonella Typhi (S. Typhi), a bacterium that causes as many as 14 million new infections and 136,000 deaths annually. Asymptomatic chronic carriers of S. Typhi play a major role in the transmission of typhoid fever, as they intermittently shed the bacteria and can unknowingly infect surrounding individuals. Here, we characterized novel compounds that target biofilm formation, a process utilized by S. Typhi to establish and maintain chronic carriage in the gallbladder, in hopes that they may be eventually used in conjunction with traditional antibiotics to prevent and/or cure chronic infections more efficiently than antibiotics alone.
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影响因子：
8
作者：
Goodman, S. D.;Obergfell, K. P.;Bakaletz, L. O.
通讯作者：
Bakaletz, L. O.
影响因子：
4.6
作者：
Goodwine, James;Gil, Joel;Sauer, Karin
通讯作者：
Sauer, Karin
DOI：
10.1016/j.ddtec.2014.02.003
发表时间：
2014-03-01
期刊：
Drug discovery today. Technologies
影响因子：
--
作者：
Jolivet-Gougeon, Anne;Bonnaure-Mallet, Martine
通讯作者：
Bonnaure-Mallet, Martine
影响因子：
6.7
作者：
Li Y;Petrova OE;Su S;Lau GW;Panmanee W;Na R;Hassett DJ;Davies DG;Sauer K
通讯作者：
Sauer K
影响因子：
4.8
作者：
Burda WN;Brenneman KE;Gonzales A;Curtiss R 3rd
通讯作者：
Curtiss R 3rd