Temporal genome-wide fitness analysis ofMycobacterium marinumduring infection reveals genetic requirement for virulence and survival in amoebae and microglial cells

Author:

Lefrançois Louise H.ORCID,Nitschke JahnORCID,Panis GaëlORCID,Prados JulienORCID,Butler Rachel E.ORCID,Mendum Tom A.ORCID,Hanna NabilORCID,Stewart Graham R.ORCID,Soldati ThierryORCID

Abstract

ABSTRACTTuberculosis remains the most pervasive infectious disease and the recent emergence of multiple or even fully drug-resistant strains increases the risk and emphasizes the need for more efficient and better drug treatments. A key feature of mycobacteria pathogenesis is the metabolic switch during infection and expression of virulence genes is often adapted to specific infection conditions. This study aims to identify genes that are involved in the establishment and maintenance of the infection. To answer these questions, we have applied Transposon Sequencing (Tn-Seq) inM. marinum, an unbiased genome-wide strategy that combines saturation insertional mutagenesis and high throughput sequencing. This approach allowed us to precisely identify the localization and relative abundance of insertions in pools of Tn mutants. The essentiality and fitness cost, in terms of growth advantage and disadvantage of over 105mutants were quantitatively compared betweenin vitroand different stages of infection in two evolutionary distinct hosts,D. discoideumand BV2 microglial cells. We found that 57% of TA sites in theM. marinumgenome were disrupted and that 568 genes (10.2%) are essential forM. marinum, which is comparable to previous Tn-Seq studies onM. tuberculosis. The major pathways involved in the survival ofM. marinumduring infection ofD. discoideumwere related to vitamin metabolism, theesx-1operon, as well as the mce1 operon.

Publisher

Cold Spring Harbor Laboratory

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