Insights from the Genome Sequence of Mycobacterium lepraemurium : Massive Gene Decay and Reductive Evolution

Author:

Benjak Andrej1ORCID,Honap Tanvi P.2,Avanzi Charlotte1,Becerril-Villanueva Enrique3,Estrada-García Iris4,Rojas-Espinosa Oscar4,Stone Anne C.56,Cole Stewart T.1

Affiliation:

1. Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

2. School of Life Sciences, Arizona State University, Tempe, Arizona, USA

3. Departamento de Psicoinmunología, Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City, Mexico

4. Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico

5. School of Human Evolution and Social Change, Arizona State University, Tempe, Arizona, USA

6. Center for Evolution and Medicine, Arizona State University, Tempe, Arizona, USA

Abstract

ABSTRACT Mycobacterium lepraemurium is the causative agent of murine leprosy, a chronic, granulomatous disease similar to human leprosy. Due to the similar clinical manifestations of human and murine leprosy and the difficulty of growing both bacilli axenically, Mycobacterium leprae and M. lepraemurium were once thought to be closely related, although it was later suggested that M. lepraemurium might be related to Mycobacterium avium . In this study, the complete genome of M. lepraemurium was sequenced using a combination of PacBio and Illumina sequencing. Phylogenomic analyses confirmed that M. lepraemurium is a distinct species within the M. avium complex (MAC). The M. lepraemurium genome is 4.05 Mb in length, which is considerably smaller than other MAC genomes, and it comprises 2,682 functional genes and 1,139 pseudogenes, which indicates that M. lepraemurium has undergone genome reduction. An error-prone repair homologue of the DNA polymerase III α-subunit was found to be nonfunctional in M. lepraemurium , which might contribute to pseudogene formation due to the accumulation of mutations in nonessential genes. M. lepraemurium has retained the functionality of several genes thought to influence virulence among members of the MAC. IMPORTANCE Mycobacterium lepraemurium seems to be evolving toward a minimal set of genes required for an obligatory intracellular lifestyle within its host, a niche seldom adopted by most mycobacteria, as they are free-living. M. lepraemurium could be used as a model to elucidate functions of genes shared with other members of the MAC. Its reduced gene set can be exploited for studying the essentiality of genes in related pathogenic species, which might lead to discovery of common virulence factors or clarify host-pathogen interactions. M. lepraemurium can be cultivated in vitro only under specific conditions and even then with difficulty. Elucidating the metabolic (in)capabilities of M. lepraemurium will help develop suitable axenic media and facilitate genetic studies.

Funder

Fondation Raoul Follereau and the Swiss National Science Foundation

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference29 articles.

1. Rojas-Espinosa O . 2009. Murine leprosy revisited, p 97–140. InTomiokaH (ed), Current topics on the profiles of host immunological response to mycobacterial infections, 1st ed.Research Signpost, Trivandrum, Kerala, India.

2. Zabolevanija u krys, vyzvannyja kislotoupornoj palotsjkoj;Stefansky WK;Rus Vratsj,1902

3. Recherches sur la lèpre: la lèpre des rats (Lepra murium);Marchoux E;Ann Inst Pasteur,1912

4. A disease of the rat caused by an acid-fast bacillus;Dean G;Cent F Bakteriol,1903

5. Feline leprosy due to Mycobacterium lepraemurium: Further clinical and molecular characterisation of 23 previously reported cases and an additional 42 cases

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