2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica.
2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica.
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DOI：
10.1002/cbic.202000422
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发表时间：
2020-12-11
期刊：
影响因子：
--
通讯作者：
May JF
中科院分区：
文献类型：
--
作者：
Thielen MK;Vaneerd CK;Goswami M;Carlson EE;May JF
对抗抗生素耐药性细菌的一个有希望的策略是开发出化合物，阻止细菌对先天免疫系统产生的抗菌条件的防御。肠沙门氏菌可引起食源性胃肠炎和伤寒，它需要组氨酸激酶(HKS)来抵抗天然免疫防御，如阳离子抗菌肽(CAMP)。在此，我们报告了2-氨基苯并噻唑阻断鼠伤寒沙门氏菌血清型中依赖组氨酸激酶的表型。我们发现，2-氨基苯并噻唑在低镁离子下抑制生长，这是一种需要组氨酸激酶介导的反应的应激条件，并减少了毒力基因PagC和PagK的表达。此外，我们还发现2-氨基苯并噻唑能减弱沙门氏菌对多粘菌素B和多粘菌素E的耐药性，这两种抗生素是最后一线抗生素，也是宿主防御阵营的模式。这些发现增加了2-氨基苯并噻唑可以阻断HK介导的细菌防御的可能性，并可以与多粘菌素联合用于治疗沙门氏菌引起的感染。防御：肠道沙门氏菌必须抵抗感染过程中遇到的抗菌条件，才能引起食源性疾病或伤寒。我们发现了一类小分子，2-氨基苯并噻唑，它能抑制某些毒力基因的表达，并减弱沙门氏菌对多粘菌素抗菌肽的耐药性。这些发现表明，这些化合物可以阻止沙门氏菌对宿主免疫防御的抵抗。
One promising strategy to combat antibiotic-resistant bacteria is to develop compounds that block bacterial defenses against antibacterial conditions produced by the innate immune system. Salmonella enterica, which causes food-borne gastroenteritis and typhoid fever, requires histidine kinases (HKs) to resist innate immune defenses such as cationic antimicrobial peptides (CAMPs). Herein, we report that 2-aminobenzothiazoles block histidine kinase-dependent phenotypes in Salmonella enterica serotype Typhimurium. We found that 2-aminobenzothiazoles inhibited growth under low Mg2+, a stressful condition that requires histidine kinase-mediated responses, and decreased expression of the virulence genes pagC and pagK. Furthermore, we discovered that 2-aminobenzothiazoles weaken Salmonella’s resistance to polymyxin B and polymyxin E, which are last-line antibiotics and models for host defense CAMPs. These findings raise the possibilities that 2-aminobenzothiazoles can block HK-mediated bacterial defenses and can be used in combination with polymyxins to treat infections caused by Salmonella. For the defense: Salmonella enterica must fight antibacterial conditions encountered during an infection in order to cause food-borne illness or typhoid fever. We discovered a class of small molecules, 2-aminobenzothiazoles, that inhibit the expression of certain virulence genes and weaken Salmonella’s resistance to polymyxin antimicrobial peptides. The findings suggest that these compounds can block Salmonella resistance to host immune defenses.
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DOI：
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