Glycerol monolaurate inhibits virulence factor production in Bacillus anthracis.

Glycerol monolaurate inhibits virulence factor production in Bacillus anthracis.
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单月桂酸甘油酯抑制炭疽杆菌毒力因子的产生。

DOI:
10.1128/aac.49.4.1302-1305.2005
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发表时间:
2005
期刊:
Antimicrobial agents and chemotherapy.
影响因子:
--
通讯作者:
Schlievert,PatrickM
Schlievert,PatrickM
中科院分区:
--
文献类型:
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作者:
Vetter,SaraM;Schlievert,PatrickM

文献摘要

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由于2001年的生物恐怖袭击,由炭疽杆菌引起的炭疽病引起了公众的注意。然而,炭疽是一种对美国农业以及欧洲、中国、非洲和澳大利亚人口构成威胁的疾病。甘油单月桂酸酯(GML)是一种已被证明可以抑制金黄色葡萄球菌和其他革兰氏阳性细菌产生外毒素的化合物。在此,我们研究了GML对B.炭疽病Sterne株B.用0、10、15或20 μg/ml的GML使炭疽菌生长至指数期后,然后定量测定保护性抗原(PA)和致死因子(LF)。8h后,浓度大于20 μg/ml的GML对微生物的生长具有抑菌作用。然而,10 μg/ml浓度的GML对生长没有抑制作用,但产生的PA和LF的量大大减少。这种影响是不是全球所有的蛋白质时,总分泌的蛋白质从培养液进行了检查,十二烷基硫酸钠-聚丙烯酰胺凝胶电泳。通过定量逆转录-PCR分析,这种毒素抑制作用显示发生在转录水平,因为pagA(PA)、lef(LF)和cya(水肿因子)的mRNA量减少。令人惊讶的是,在GML存在的情况下,atxA(外毒素基因表达的调节因子)的mRNA水平上升。这些数据将有助于开发治疗工具来治疗炭疽病,无论是在动物还是人类身上。这些结果也表明,毒力调节机制存在独立的atxA。
Anthrax, caused byBacillus anthracis, has been brought to the public's attention because of the 2001 bioterrorism attacks. However, anthrax is a disease that poses agricultural threats in the United States as well as human populations in Europe, China, Africa, and Australia. Glycerol monolaurate (GML) is a compound that has been shown to inhibit exotoxin production byStaphylococcus aureusand other gram-positive bacteria. Here, we study the effects of GML on growth and toxin production inB. anthracis. The Sterne strain ofB. anthraciswas grown to post-exponential phase with 0-, 10-, 15-, or 20-μg/ml concentrations of GML and then assayed quantitatively for protective antigen (PA) and lethal factor (LF). After 8 h, GML at concentrations greater than 20 μg/ml was bacteriostatic to growth of the organism. However, a 10-μg/ml concentration of GML was not growth inhibitory, but amounts of PA and LF made were greatly reduced. This effect was not global for all proteins when total secreted protein from culture fluids was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Through quantitative reverse transcription-PCR assays, this toxin-inhibitory effect was shown to occur at the transcriptional level, since amounts of mRNA forpagA(PA),lef(LF), andcya(edema factor) were reduced. Surprisingly, mRNA levels ofatxA, a regulator of exotoxin gene expression, rose in the presence of GML. These data will be useful in developing therapeutic tools to treat anthrax disease, whether in animals or humans. These results also suggest that mechanisms of virulence regulation exist independent ofatxA.