New inhibitors of colony spreading in Bacillus subtilis and Bacillus anthracis.
New inhibitors of colony spreading in Bacillus subtilis and Bacillus anthracis.
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DOI：
10.1016/j.bmcl.2011.06.082
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发表时间：
2011-09-15
影响因子：
2.7
通讯作者：
Sammakia, Tarek
中科院分区：
文献类型：
--
作者：
Hao, Xin;Tam Nguyen;Kearns, Daniel B.;Arpin, Carolynn C.;Fall, Ray;Sammakia, Tarek
关键词：
我们最近对缺乏功能鞭毛的枯草芽孢杆菌菌株的滑动运动进行了表征，并在此描述了在这些菌株中发现了菌落扩散的抑制剂以及凝集的病原体炭疽杆菌。利用枯草芽孢杆菌菌株筛选可能抑制半固体培养基菌落扩散的新型抗菌剂。从一组不同的有机结构中，人们发现对硝基苯甘油(NPG)，一种主要用于临床实验室控制变形杆菌蜂群的试剂，可以抑制菌落扩散。合成并测试了NPG的四个立体异构体，只有1R，2S-(1R-抗)和1R，2R-(1R-syn)NPG异构体在定量集落铺展实验中具有显著的活性。合成了26个NPG类似物和相关结构，并对其进行了测试，以确定更有活性的抑制剂。对甲磺酰基苯甘油(p-SPG)被发现是最有效的化合物，但不是它的邻位或间位类似物，所有4个p-SPG立体异构体的合成和测试表明，1R-反异构体的活性最高，平均IC50值为16μM(3~5μg mL−1)。对炭疽杆菌，1R-抗SPG和1R-抗NPG的菌落扩散IC50值分别为12μM(2-4μg m L−1)和150μM。对于所测试的两种芽孢杆菌，1R-anti-SPG抑制琼脂平板上表面培养物的菌落扩散，但在液体培养物中不具有抑菌或杀菌作用。寻找NPG/SPG类化合物的细胞靶点(S)的工作正在进行中，因为这可能有助于理解菌落扩散的机制(S)，以及设计和开发更有效的抑制炭疽杆菌表面培养的药物。
We have recently characterized sliding motility in Bacillus subtilis strains that lack functional flagella, and here describe the discovery of inhibitors of colony spreading in these strains as well as the aflagellate pathogen, B. anthracis. Aflagellate B. subtilis strains were used to screen for new types of antibacterials that might inhibit colony spreading on semi-solid media. From a diverse set of organic structures, p-nitrophenylglycerol (NPG), an agent used primarily in clinical laboratories to control Proteus swarming, was found to inhibit colony spreading. The four stereoisomers of NPG were synthesized and tested, and only the 1R,2S- (1R-anti) and 1R,2R- (1R-syn) NPG isomers had significant activity in a quantitative colony-spreading assay. Twenty-six NPG analogs and related structures were synthesized and tested to identify more active inhibitors. p-Methylsulfonylphenylglycerol (p-SPG), but not its ortho or meta analogs, was found to be the most effective of these compounds, and synthesis and testing of all four p-SPG stereoisomers showed that the 1R-anti-isomer was the most active with an average IC50 of 16 μM (3 to 5 μg mL−1). For B. anthracis, the colony-spreading IC50 values for 1R-anti-SPG and 1R-anti-NPG are 12 μM (2–4 μg mL−1) and >150 μM, respectively. For both Bacillus species tested, 1R-anti-SPG inhibits colony spreading of surface cultures on agar plates, but is not bacteriostatic or bacteriocidal in liquid cultures. Work is in progress to find the cellular target(s) of the NPG/SPG class of compounds, since this could lead to an understanding of the mechanism(s) of colony spreading as well as design and development of more potent inhibitors for the control of B. anthracis surface cultures.
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影响因子：
4.4
作者：
Borlee, Bradley R.;Geske, Grant D.;Handelsman, Jo
通讯作者：
Handelsman, Jo
影响因子：
3
作者：
Liaw, SJ;Lai, HC;Wang, WB
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一种定义的培养基，以研究枯草芽孢杆菌中无鞭毛突变体中的滑动运动。
影响因子：
4.2
作者：
Fall, Ray;Kearns, Daniel B.;Nguyen, Tam
通讯作者：
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影响因子：
2.1
作者：
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通讯作者：
Torres, RR
影响因子：
4.4
作者：
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通讯作者：
Kelley, Lynda C.