dictyNews

Electronic Edition

Volume 50, number 1

January 26, 2024



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Abstracts

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Temporal genome-wide fitness analysis of Mycobacterium marinum 

during infection reveals the genetic requirement for virulence and 

survival in amoebae and microglial cells



Louise H Lefrançois1#, Jahn Nitschke1#, Huihai Wu2, Gaël Panis3, 

Julien Prados3,4, Rachel E Butler2, Tom A Mendum2, Nabil Hanna1*, 

Graham R Stewart2, Thierry Soldati1*



1Department of Biochemistry, Faculty of Science, University of Geneva, 

30 Quai Ernest-Ansermet, Science II, 1211 Geneva-4, Switzerland

2Department of Microbial Sciences, School of Biosciences, University 

of Surrey, Guildford, Surrey GU2 7XH, UK

3Department of Microbiology and Molecular Medicine, Institute of 

Genetics and Genomics in Geneva (iGE3), Faculty of Medicine/CMU, 

University of Geneva, Rue Michel-Servet 1, 1211 Genève 4, Switzerland

4Bioinformatics Support Platform for data analysis, Geneva University, 

Medicine Faculty, Geneva, Switzerland.



# Contributed equally to the work



*Co-corresponding authors





mSystems : 

https://journals.asm.org/doi/epub/10.1128/msystems.01326-23



Tuberculosis remains the most pervasive infectious disease and recent 

emergence of drug-resistant strains emphasizes the need for more 

efficient drug treatments. A key feature of pathogenesis, conserved 

between the human pathogen Mycobacterium tuberculosis and the 

model pathogen Mycobacterium marinum, is the metabolic switch to lipid 

catabolism and altered expression of virulence genes at different stages 

of infection. This study aims at identifying genes involved in sustaining 

viable intracellular infection. We applied Transposon Sequencing (Tn-Seq) 

to M. marinum, an unbiased genome-wide strategy combining saturation 

insertional mutagenesis and high throughput sequencing. This approach 

allowed us to identify the localization and relative abundance of insertions 

in pools of transposon mutants. Gene essentiality and fitness cost of 

mutations were quantitatively compared between in vitro growth and 

different stages of infection in two evolutionary distinct phagocytes, the 

amoeba Dictyostelium discoideum and the murine BV2 microglial cells. In 

the M. marinum genome, 57% of TA sites were disrupted and 568 genes 

(10.2%) were essential, which is comparable to previous Tn-Seq studies 

on M. tuberculosis and M. bovis. Major pathways involved in the survival 

of M. marinum during infection of D. discoideum are related to DNA 

damage repair, lipid and vitamin metabolism, the type VII secretion system 

(T7SS) ESX-1 and the Mce1 lipid transport system. These pathways except 

Mce1 and some glycolytic enzymes, were similarly affected in BV2 cells. 

These differences suggest subtly distinct nutrient availability or requirement 

in different host cells despite the known predominant use of lipids in both 

amoeba and microglial cells.





Submitted by Thierry Soldati [[log in to unmask]]

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[End dictyNews, volume 50, number 1]