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粘细菌索莱福菌素代谢产物卡罗他汀对变形链球菌生物膜的破坏作用

Damage of Streptococcus mutans biofilms by carolacton, a secondary metabolite from the myxobacterium Sorangium cellulosum.

机构信息

Helmholtz-Centre for Infection Research, Braunschweig, Germany.

出版信息

BMC Microbiol. 2010 Jul 26;10:199. doi: 10.1186/1471-2180-10-199.

Abstract

BACKGROUND

Streptococcus mutans is a major pathogen in human dental caries. One of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. Eradication of such biofilms is extremely difficult. We therefore screened a library of secondary metabolites from myxobacteria for their ability to damage biofilms of S. mutans.

RESULTS

Here we show that carolacton, a secondary metabolite isolated from Sorangium cellulosum, has high antibacterial activity against biofilms of S. mutans. Planktonic growth of bacteria was only slightly impaired and no acute cytotoxicity against mouse fibroblasts could be observed. Carolacton caused death of S. mutans biofilm cells, elongation of cell chains, and changes in cell morphology. At a concentration of 10 nM carolacton, biofilm damage was already at 35% under anaerobic conditions. A knock-out mutant for comD, encoding a histidine kinase specific for the competence stimulating peptide (CSP), was slightly less sensitive to carolacton than the wildtype. Expression of the competence related alternate sigma factor ComX was strongly reduced by carolacton, as determined by a pcomX luciferase reporter strain.

CONCLUSIONS

Carolacton possibly interferes with the density dependent signalling systems in S. mutans and may represent a novel approach for the prevention of dental caries.

摘要

背景

变形链球菌是人类龋齿的主要病原体。其重要的毒力特性之一是能够在牙齿表面形成生物膜(牙菌斑)。消除这种生物膜极其困难。因此,我们从粘细菌的次级代谢产物文库中筛选出能够破坏变形链球菌生物膜的物质。

结果

我们发现,来源于粘细菌的次级代谢产物卡罗他汀对变形链球菌生物膜具有很强的抗菌活性。浮游细菌的生长仅受到轻微抑制,且对小鼠成纤维细胞没有明显的急性细胞毒性。卡罗他汀导致变形链球菌生物膜细胞死亡、细胞链伸长和细胞形态改变。在 10 nM 的卡罗他汀浓度下,在厌氧条件下生物膜破坏率已达到 35%。编码特定于感应肽(CSP)的组氨酸激酶的 comD 敲除突变体对卡罗他汀的敏感性略低于野生型。卡罗他汀强烈抑制与感受态相关的替代 σ 因子 ComX 的表达,这可以通过 pcomX 荧光素酶报告菌株来确定。

结论

卡罗他汀可能干扰了变形链球菌中密度依赖的信号系统,可能代表了预防龋齿的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d303/2915981/8b55e51d63cf/1471-2180-10-199-1.jpg

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