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在鼠口腔黏膜中占主导地位,具有几丁质酶活性,会损害真菌细胞壁的完整性。

is a dominant in the murine oral mucosa and has chitinase activity that compromises fungal cell wall integrity.

机构信息

Department of General Dentistry, the University of Connecticut Health Center, Farmington, Connecticut, USA.

出版信息

mBio. 2024 Oct 16;15(10):e0241624. doi: 10.1128/mbio.02416-24. Epub 2024 Sep 17.

DOI:10.1128/mbio.02416-24
PMID:39287438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11481578/
Abstract

UNLABELLED

The oral microbiome is a critical determinant of health and disease, as interactions between oral microorganisms can influence their physiology and the development or severity of oral infections. Lactobacilli have a widely recognized antagonistic relationship with and may exhibit probiotic properties that limit oral fungal infection. We previously reported that strain MT4, an oral strain isolated from C57BL/6 mice, can induce global changes in the murine oral microbiome and has anti- activity . To build on this information, we analyzed its abundance on the mouse oral mucosa, tested its impact on the severity and progression of oropharyngeal candidiasis (OPC) in a mouse model, and further explored the mechanism of antifungal activity . Our findings reveal that MT4 is a dominant cultivable in the oral mucosa of C57BL/6 mice. Strain MT4 has chitinase activity against , which damages the cell wall and compromises fungal metabolic activity. Oral inoculation with strain MT4 causes a reduction in the -induced rise in the abundance of oral enterococci and oral mucosal damage. This research underscores the potential of strain MT4 as a novel probiotic agent in the prevention or management of OPC, and it contributes to a better understanding of the role of oral bacterial microbiota role in the pathogenesis of fungal infections.

IMPORTANCE

The interactions between the opportunistic pathogen and resident oral bacteria are particularly crucial in maintaining oral health. Emerging antifungal drug-resistant strains, slow-paced drug discovery, and the risk of side effects can compromise the effectiveness of current treatments available for oropharyngeal candidiasis. This study advances the search for alternative microbiome-targeted therapies in oral fungal infections. We report that strain MT4 prevents the -induced bloom of dysbiotic oral enterococci and reduces oral mucosal lesions in an oropharyngeal candidiasis murine model. We also show that this strain directly compromises the cell wall and reduces fungal metabolic activity, partly due to its chitinase activity.

摘要

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口腔微生物组是健康和疾病的关键决定因素,因为口腔微生物之间的相互作用会影响它们的生理机能以及口腔感染的发展或严重程度。乳杆菌与具有广泛公认的拮抗关系,并且可能表现出限制口腔真菌感染的益生菌特性。我们之前报道过,从 C57BL/6 小鼠中分离出来的口腔菌株 MT4 可以诱导鼠口腔微生物组的全局变化,并具有抗活性。在此基础上,我们分析了其在小鼠口腔黏膜上的丰度,测试了其在小鼠模型中对口咽念珠菌病(OPC)严重程度和进展的影响,并进一步探索了抗真菌活性的机制。我们的研究结果表明,MT4 是 C57BL/6 小鼠口腔黏膜上的主要可培养。该菌株对具有几丁质酶活性,可以破坏细胞壁并损害真菌的代谢活性。口腔接种 MT4 菌株可减少诱导的口腔肠球菌丰度升高和口腔黏膜损伤。这项研究强调了 MT4 菌株作为新型益生菌制剂在预防或管理 OPC 中的潜力,并有助于更好地了解口腔细菌微生物群在真菌感染发病机制中的作用。

重要性

机会性病原体与常驻口腔细菌之间的相互作用对于维持口腔健康尤为关键。新兴的抗真菌药物耐药菌株、缓慢的药物发现过程以及副作用的风险都可能影响目前用于口咽念珠菌病的治疗效果。这项研究推进了针对口腔真菌感染的替代微生物组靶向治疗方法的研究。我们报告称,MT4 菌株可防止诱导的失调口腔肠球菌的大量繁殖,并在口咽念珠菌病小鼠模型中减少口腔黏膜损伤。我们还表明,该菌株直接损害细胞壁并降低真菌的代谢活性,部分原因是其几丁质酶活性。

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