PT  - JOURNAL ARTICLE
AU  - Charlotte Genestet
AU  - Guislaine Refrégier
AU  - Elisabeth Hodille
AU  - Rima Zein-Eddine
AU  - Adrien Le Meur
AU  - Fiona Hak
AU  - Alexia Barbry
AU  - Emilie Westeel
AU  - Jean-Luc Berland
AU  - Astrid Engelmann
AU  - Isabelle Verdier
AU  - Gérard Lina
AU  - Florence Ader
AU  - Stéphane Dray
AU  - Laurent Jacob
AU  - François Massol
AU  - Samuel Venner
AU  - Oana Dumitrescu
AU  - the Lyon TB study group
TI  - <em>Mycobacterium tuberculosis</em> genetic features associated with pulmonary tuberculosis severity
AID  - 10.1101/2022.05.25.493361
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.25.493361
4099  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493361.short
4100  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493361.full
AB  - Mycobacterium tuberculosis (Mtb) infections result in a wide spectrum of clinical presentations but without proven Mtb genetic determinants. Herein, 234 pulmonary tuberculosis (TB) patients were stratified according to TB disease severity and Mtb genetic features were explored using whole genome sequencing, including heterologous single nucleotide polymorphism (SNP) calling to explore micro-diversity. Clinical isolates from patients with mild TB carried mutations in genes associated with host-pathogen interaction, while those from patients with moderate/severe TB carried mutations associated with regulatory mechanisms. Genome-wide association study identified a SNP in the promoter of the gene coding for the virulence regulator EspR associated with moderate/severe disease. Structural equation modelling and model comparisons indicated that TB severity was associated with the detection of Mtb micro-diversity within clinical isolates and to the espR SNP. Taken together, these results provide a new insight to better understand TB pathophysiology and could provide new prognosis tool for pulmonary TB severity.Competing Interest StatementThe authors have declared no competing interest.