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Press release Ecofect - 28 October 2022

On The October 28, 2022

Study based on the hypothesis that genetic features of Mycobacterium tuberculosis clinical isolates may be linked to TB severity.


 

Mycobacterium tuberculosis genetic features associated with pulmonary tuberculosis severity.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) complex remains one of the most prevalent and deadly infectious disease. Mtb infection results in a wide spectrum of TB clinical presentations, with an array of severity symptoms, but without proven Mtb genetic determinants. This study, developed by researchers from the International Center for Infectious Diseases (CIRI) and the Laboratory of Biometry and Evolutive Biology (LBBE), in collaboration with researchers from Paris-Saclay University and the Center for Infection and Immunity of Lille (CIIL), and financed by the Ecofect LabEx through the ViValDi project, is based on the hypothesis that genetic features of Mtb clinical isolates may be linked to TB severity.

For this purpose, 234 pulmonary TB patients diagnosed at the Lyon University Hospital were included in this study. Patients demographical and clinical data were recorded, enabling to stratify these patients according to a clinical score for TB disease severity. Mtb genetic features were explored using whole genome sequencing, including heterologous single nucleotide polymorphism (SNP) calling to explore micro-diversity. To relate TB severity to various host and bacterial explanatory variables, we performed a structural equation modelling (SEM) analysis. SEM examines the causal relationships among variables and allowed to capture the importance of a certain path of influence from cause to effect. SEM found that both the presence of Mtb micro-diversity within clinical isolates and a particular SNP, identified by genome-wide association study, led to greater clinical TB severity. These Mtb genetic features are therefore valuable candidates for new biomarkers of TB severity and could be useful to identify early-on patients at high risk of severe TB in order to ensure optimal management.

Article reference:

Mycobacterium tuberculosis genetic features associated with pulmonary tuberculosis severity.

Genestet C, Refrégier G, Hodille E, Zein-Eddine R, Meur AL, Hak F, Barbry A, Westeel E, Berland JL, Engelmann A, Verdier I, Lina G, Ader F, Dray S, Jacob L, Massol F, Venner S, Dumitrescu O; Lyon TB study group.

Int J Infect Dis. first published October 20, 2022. | Link to article

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