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松萝酸通过下调双组分信号转导系统降低变形链球菌的产酸能力、耐酸能力和葡萄糖代谢。

Usnic acid deteriorates acidogenicity, acidurance and glucose metabolism of Streptococcus mutans through downregulation of two-component signal transduction systems.

机构信息

Department of Biotechnology, Alagappa University, Science Campus, Karaikudi, Tamil Nadu, 630003, India.

出版信息

Sci Rep. 2021 Jan 14;11(1):1374. doi: 10.1038/s41598-020-80338-6.

DOI:10.1038/s41598-020-80338-6
PMID:33446778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7809355/
Abstract

The principal etiological agent of human dental caries, Streptococcus mutans is a multi-virulent pathogen that can transform commensal oral microbial community to plaque biofilms. Major virulence factors that are associated with the cariogenicity of S. mutans include adhesion, acidogenicity and acidurity. All these pathogenic traits coordinate and alter the dental plaque ecology which provide room for interaction with other similar acidogenic and aciduric bacteria. This cariogenic flora increases the possibility of enamel demineralization which headway to caries development. The present study was aimed at evaluating the antimicrobial and antiinfective potential of a lichen secondary metabolite usnic acid (UA) against S. mutans. Minimum inhibitory concentration (MIC), Minimum bactericidal concentration (MBC) and growth kinetics were evaluated to determine the antimicrobial potential of UA against S. mutans. UA at 5 µg mL and 10 µg mL concentration were considered as MIC and MBC respectively. Effect on biofilm formation was microscopically assessed and found to be reduced in a concentration dependent manner. Gene expression of gtfB, gtfC, gtfD, vicR, ComDE and smu0630 was found to be downregulated upon treatment with sub-MIC of UA. Acidogenicity, acidurity, eDNA synthesis and response to oxidative stress were found to be attenuated by the influence of UA. It was also demonstrated to act on preformed mature biofilm of S. mutans. Moreover, UA was shown to possess very low frequency to acquire spontaneous resistance development in S. mutans. Besides, no morphological aberrations or toxic effect was instigated by UA in the human buccal epithelial cells as well as to the oral commensals. Altogether, these results demonstrate the therapeutic potential of usnic acid in the treatment of S. mutans infection.

摘要

人类龋齿的主要病因细菌——变形链球菌是一种多毒力病原体,可将共生口腔微生物群落转化为菌斑生物膜。与变形链球菌致龋性相关的主要毒力因子包括黏附性、产酸性和耐酸性。所有这些致病特征协调并改变了牙菌斑的生态环境,为与其他类似产酸和耐酸细菌的相互作用提供了空间。这种致龋菌群增加了釉质脱矿的可能性,从而导致龋齿的发展。本研究旨在评估地衣次级代谢产物——松萝酸(UA)对变形链球菌的抗菌和抗感染潜力。评估最小抑菌浓度(MIC)、最小杀菌浓度(MBC)和生长动力学,以确定 UA 对变形链球菌的抗菌潜力。UA 在 5 μg/mL 和 10 μg/mL 浓度下被认为是 MIC 和 MBC。通过显微镜评估对生物膜形成的影响,发现其呈浓度依赖性降低。发现基因表达 gtfB、gtfC、gtfD、vicR、ComDE 和 smu0630 受到 UA 亚 MIC 处理的下调。产酸、耐酸、eDNA 合成和对氧化应激的反应均因 UA 的影响而减弱。还证明它可以作用于变形链球菌已形成的成熟生物膜。此外,UA 在变形链球菌中获得自发耐药发展的频率非常低。此外,UA 对人颊上皮细胞和口腔共生菌既没有引起形态异常,也没有引起毒性作用。总的来说,这些结果表明松萝酸在治疗变形链球菌感染方面具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/0667056c662a/41598_2020_80338_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/f0964f510523/41598_2020_80338_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/10a0b567b21d/41598_2020_80338_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/513b618e98e2/41598_2020_80338_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/7c39db9dd1fa/41598_2020_80338_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/c6dde7ced487/41598_2020_80338_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/0412754f0ae1/41598_2020_80338_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/0667056c662a/41598_2020_80338_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/f0964f510523/41598_2020_80338_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/10a0b567b21d/41598_2020_80338_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/513b618e98e2/41598_2020_80338_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/7c39db9dd1fa/41598_2020_80338_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/c6dde7ced487/41598_2020_80338_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/0412754f0ae1/41598_2020_80338_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bef5/7809355/0667056c662a/41598_2020_80338_Fig9_HTML.jpg

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