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MraZ对……致病性的功能见解

Functional Insights of MraZ on the Pathogenicity of .

作者信息

Wang Bingjie, Duan Jingjing, Jin Ye, Zhan Qing, Xu Yanlei, Zhao Huilin, Wang Xinyi, Rao Lulin, Guo Yinjuan, Yu Fangyou

机构信息

Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.

Department of Clinical Laboratory, Renmin Hospital, Hubei University of Medicine, Hubei, People's Republic of China.

出版信息

Infect Drug Resist. 2021 Nov 2;14:4539-4551. doi: 10.2147/IDR.S332777. eCollection 2021.

DOI:10.2147/IDR.S332777
PMID:34754202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8572050/
Abstract

INTRODUCTION

In recent years, multidrug-resistant methicillin-resistant has become increasingly prevalent, which raised a huge challenge to antibiotic treatment of infectious diseases. The anti-virulence strategy targeting virulent factors is a promising novel therapy for infection. The virulence mechanism of was needed to explore deeply to develop more targets and improve the effectiveness of anti-virulence strategies.

RESULTS

In this study, we found was highly conserved in , and its production is homologous with the MraZ of , a transcriptional regulator involved in the growth and cell division of . To investigate the function of in , we constructed a MW2 deletion mutant and its complementary mutant for virulence comparison. Although no remarkable influence on the growth, the deletion mutant led to significantly reduced resistance to human neutrophils and decreased virulence in model as well as mouse skin and soft tissue infection models, indicating its essential contribution to virulence and immune evasion to support the pathogenicity of infection. RNA-Seq and quantitative RT-qPCR revealed that MraZ is a multi-functional regulator; it involves in diverse biological processes and can up-regulate the expression of various virulence genes by and .

CONCLUSION

plays vital roles in the pathyogenicity of via regulating many virulence genes. It may be an attractive target for anti-virulence therapy of .

摘要

引言

近年来，多重耐药的耐甲氧西林金黄色葡萄球菌日益普遍，这给传染病的抗生素治疗带来了巨大挑战。针对毒力因子的抗毒力策略是一种有前景的新型感染治疗方法。需要深入探索金黄色葡萄球菌的毒力机制，以开发更多靶点并提高抗毒力策略的有效性。

结果

在本研究中，我们发现MraZ在金黄色葡萄球菌中高度保守，其产生与参与金黄色葡萄球菌生长和细胞分裂的转录调节因子枯草芽孢杆菌的MraZ同源。为了研究MraZ在金黄色葡萄球菌中的功能，我们构建了MW2 MraZ缺失突变体及其互补突变体用于毒力比较。尽管对生长没有显著影响，但MraZ缺失突变体导致对人中性粒细胞的抗性显著降低，并且在全血模型以及小鼠皮肤和软组织感染模型中的毒力降低，表明其对毒力和免疫逃避以支持金黄色葡萄球菌感染的致病性有重要贡献。RNA测序和定量逆转录-定量聚合酶链反应显示MraZ是一种多功能调节因子；它参与多种生物学过程，并可通过[具体方式1]和[具体方式2]上调各种毒力基因的表达。

结论

MraZ通过调节许多毒力基因在金黄色葡萄球菌的致病性中起重要作用。它可能是金黄色葡萄球菌抗毒力治疗的一个有吸引力的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/a044ede72b86/IDR-14-4539-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/89c322c6e5b1/IDR-14-4539-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/69cb29e12d09/IDR-14-4539-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/811b2794bce1/IDR-14-4539-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/3763019e0fdc/IDR-14-4539-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/0aeab5403ca1/IDR-14-4539-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/8548a1823c61/IDR-14-4539-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/1b63bcdd9ed8/IDR-14-4539-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/a044ede72b86/IDR-14-4539-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/89c322c6e5b1/IDR-14-4539-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/69cb29e12d09/IDR-14-4539-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/811b2794bce1/IDR-14-4539-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/3763019e0fdc/IDR-14-4539-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/0aeab5403ca1/IDR-14-4539-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/8548a1823c61/IDR-14-4539-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/1b63bcdd9ed8/IDR-14-4539-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/8572050/a044ede72b86/IDR-14-4539-g0008.jpg

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