GlfT1 down-regulation affects Mycobacterium tuberculosis biofilm formation and its in-vitro and in-vivo survival - 20/07/23
![](/templates/common/images/mail.png)
Abstract |
Mycobacterial galactan biosynthesis is critical for cell viability and growth, therefore an effort was made to study galactofuranosyl transferase 1, encoded by MRA_3822 in Mycobacterium tuberculosis H37Ra (Mtb-Ra). Galactofuranosyl transferases are involved in the biosynthesis of mycobacterial cell wall galactan chain and have been shown to be essential for in-vitro growth of Mycobacterium tuberculosis. In Mtb-Ra and Mycobacterium tuberculosis H37Rv (Mtb-Rv), two galactofuranosyl transferases are present, GlfT1 acts as initiator of galactan biosynthesis and GlfT2 continues with the subsequent polymerization events. GlfT2 has been well studied however GlfT1 inhibition/down-regulation and its effect on mycobacterial survival fitness has not been evaluated. To study the Mtb-Ra survival after GlfT1 silencing, Mtb-Ra knockdown and complemented strains were developed. In this study we show that GlfT1 down-regulation leads to increased susceptibility to ethambutol. Expression of glfT1 was up-regulated in the presence of ethambutol, and also in the presence of oxidative and nitrosative stress and upon exposure to low pH. Also, reduced biofilm formation, increased accumulation of ethidium bromide, and reduced tolerance to peroxide, nitric oxide and acid stress, were observed. The present study also demonstrates that GlfT1 down-regulation leads to reduced survival of Mtb-Ra in macrophages and in mice.
Le texte complet de cet article est disponible en PDF.Keywords : Mycobacterium tuberculosis, Galactofuranosyl transferase, Ethambutol susceptibility, Biofilm formation, In-vitro and ex-vivo survival
Abbreviations : Wild-type, Knockdown, Knockdown with complementation, Mycobacterium tuberculosis H37Ra, galactofuranosyl transferase 1, galactofuranosyl transferase 2, Fetal bovine serum, Microtiter Alamar Blue Assay, Ethidium bromide, Nile red, Propidium iodide, Immunofluorescence, Arabinogalactan
Plan
Vol 141
Article 102352- juillet 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?