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Epigallocatechin gallate inhibits leukotoxin release by Aggregatibacter actinomycetemcomitans by promoting association with the bacterial membrane
Molecular Oral Microbiology ( IF 3.7 ) Pub Date : 2019-12-26 , DOI: 10.1111/omi.12275
En Hyung Chang 1 , Peter Giaquinto 1 , Joanne Huang 1 , Nataliya V Balashova 2 , Angela C Brown 1
Affiliation  

The oral pathogen, Aggregatibacter actinomycetemcomitans, produces a number of virulence factors, including a leukotoxin (LtxA), which specifically kills human white blood cells, to provide a colonization advantage to the bacterium. Strains of A. actinomycetemcomitans that produce more LtxA have been more closely linked to disease, indicating that this toxin plays a key role in pathogenesis of the bacterium. Disruption of the activity of LtxA thus represents a promising approach to reducing the pathogenicity of the bacterium. Catechins are polyphenolic molecules derived from plants, which have shown potent antibacterial and antitoxin activities. We have previously shown that galloylated catechins are able to prevent LtxA delivery to host cells by altering the toxin's secondary structure and preventing binding to cholesterol on the host cell membrane. Here, we have investigated how one particular galloylated catechin, epigallocatechin gallate (EGCg), affects A. actinomycetemcomitans growth and toxin secretion. Our results demonstrate that EGCg, at micromolar concentrations, inhibits A. actinomycetemcomitans growth, as has been reported for other bacterial species. At subinhibitory concentrations, EGCg promotes LtxA production, but the toxicity of the bacterial supernatant against human immune cells is reduced. The results of our biophysical studies indicate that this seemingly contradictory result is caused by an EGCg‐mediated enhancement of LtxA affinity for the bacterial cell surface. Together, these results demonstrate the potential of EGCg in the treatment of virulent A. actinomycetemcomitans infections.

中文翻译:

表没食子儿茶素没食子酸酯通过促进与细菌膜的缔合来抑制聚合酶放线菌引起的白细胞毒素释放

口腔病原体放线杆菌聚合酶(Aggregatibacter actinomycetemcomitans)产生许多毒力因子,包括白细胞毒素(LtxA),该因子可特异性杀死人类白细胞,从而为细菌提供定殖优势。放线菌的菌株产生更多LtxA的细菌与疾病的联系更为紧密,表明该毒素在细菌的发病机理中起关键作用。因此,破坏LtxA的活性代表了减少细菌致病性的一种有前途的方法。儿茶素是植物衍生的多酚分子,具有强大的抗菌和抗毒素活性。先前我们已经表明,没食子酸酯化的儿茶素能够通过改变毒素的二级结构并防止与宿主细胞膜上的胆固醇结合,从而阻止LtxA传递至宿主细胞。在这里,我们研究了一种没食子儿茶素没食子儿茶素没食子酸酯(EGCg)如何影响A.放线菌生长和毒素分泌。我们的结果表明,以微摩尔浓度计的EGCg可以抑制A.放线菌的生长,正如其他细菌物种所报道的那样。在亚抑制浓度下,EGCg促进LtxA产生,但细菌上清液对人免疫细胞的毒性降低。我们的生物物理研究结果表明,这种看似矛盾的结果是由EGCg介导的LtxA对细菌细胞表面亲和力增强引起的。总之,这些结果证明了EGCg在治疗强毒放线放线杆菌感染中的潜力。
更新日期:2019-12-26
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