Mycobacterium tuberculosis PE_PGRS38 Enhances Intracellular Survival of Mycobacteria by Inhibiting TLR4/NF-κB-Dependent Inflammation and Apoptosis of the Host

Author:

Ullah Hayan12,Shi Xiaoxia3,Taj Ayaz1,Cheng Lin1,Yan Qiulong2,Sha Shanshan1,Ahmad 4,Kang Jian1,Haris Muhammad1,Ma Xiaochi5ORCID,Ma Yufang12ORCID

Affiliation:

1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China

2. Department of Microbiology, Dalian Medical University, Dalian 116044, China

3. Department of Experimental Teaching Center of Public Health, Dalian Medical University, Dalian 116044, China

4. Department of Immunology, Dalian Medical University, Dalian 116044, China

5. Pharmaceutical Research Center, The Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China

Abstract

Mycobacterium tuberculosis (Mtb) ranks as the most lethal human pathogen, able to fend off repeated attacks by the immune system or medications. PE_PGRS proteins are hallmarks of the pathogenicity of Mtb and contribute to its antigenic diversity, virulence, and persistence during infection. M. smegmatis is a nonpathogenic mycobacterium that naturally lacks PE_PGRS and is used as a model to express Mtb proteins. PE_PGRS has the capability to evade host immune responses and enhance the intracellular survival of M. smegmatis. Despite the intense investigations into PE_PGRS proteins, their role in tuberculosis remains elusive. We engineered the recombinant M. smegmatis strain Ms-PE_PGRS38. The result shows that PE_PGRS38 is expressed in the cell wall of M. smegmatis. PE_PGRS38 contributes to biofilm formation, confers permeability to the cell wall, and shows variable responses to exogenous stresses. PE_PGRS38 downregulated TLR4/NF-κB signaling in RAW264.7 macrophages and lung tissues of infected mice. In addition, PE_PGRS38 decreased NLRP3-dependent IL-1β release and limited pathogen-mediated inflammasome activity during infection. Moreover, PE_PGRS38 inhibited the apoptosis of RAW264.7 cells by downregulating the expression of apoptotic markers including Bax, cytochrome c, caspase-3, and caspase-9. In a nutshell, our findings demonstrate that PE_PGRS38 is a virulence factor for Mtb that enables recombinant M. smegmatis to survive by resisting and evading the host’s immune responses during infection.

Funder

National Natural Science Foundation of China

Publisher

MDPI AG

Reference67 articles.

1. The history of tuberculosis: From the first historical records to the isolation of Koch’s bacillus;Barberis;J. Prev. Med. Hyg.,2017

2. WHO (2022). Global Tuberculosis Report, WHO.

3. Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: Evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other;Tundup;FEBS Lett.,2006

4. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence;Cole;Nature,1998

5. The PE multigene family: A ‘molecular mantra’for mycobacteria;Brennan;Trends Microbiol.,2002

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3