Cholesterol plays a larger role during Mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2017-03, Vol.103, p.1-9
• Main Authors: Soto-Ramirez, Maria D, Aguilar-Ayala, Diana A, Garcia-Morales, Lazaro, Rodriguez-Peredo, Sofia M, Badillo-Lopez, Claudia, Rios-Muñiz, Diana E, Meza-Segura, Mario A, Rivera-Morales, Gelen Y, Leon-Solis, Lizbel, Cerna-Cortes, Jorge F, Rivera-Gutierrez, Sandra, Helguera-Repetto, Addy C, Gonzalez-y-Merchand, Jorge A
• Format: Article
• Language: English
• Subjects: Activation; Adaptation; Bacilli; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carbon sources; Cholesterol; Cholesterol - metabolism; Dormancy; Energy Metabolism; Fatty acids; Fatty Acids - metabolism; Gene expression; Gene Expression Regulation, Bacterial; Hypoxia; Infectious Disease; Latent Tuberculosis - metabolism; Latent Tuberculosis - microbiology; Lipids; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - growth & development; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Oxygen - metabolism; Pulmonary/Respiratory; Reactivation; Signal Transduction; Tuberculosis; Ventilation; Virulence
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2016.12.004

Abstract It is known that cholesterol plays a key role for Mycobacterium tuberculosis ( Mtb ) adaptation and survival within the host, thus contributing to the establishment of dormancy. It has been extensively demonstrated that fatty acids are the main energy source of Mtb during infection and dormancy, and it has been proposed that these molecules are implicated in reactivation of bacilli from a dormant state. We used in vitro models to analyze Mtb gene expression during dormancy and reactivation when fatty acids and cholesterol are the unique carbon source in the media. Our results suggest that cholesterol might function as a signal to trigger Mtb expression of some genes required for stress protection earlier than the one induced by fatty acids alone, indicating that cholesterol is very favorable for its development. This process is so conducive that cholesterol-adapted bacilli can reactivate their growth after NRP2 dormancy state even 10 min post ventilation. Thus, we hypothesize that cholesterol is not only involved in Mtb dormancy but that it also plays a critical role for favorable and almost immediate reactivation from an in vitro long-lasting dormant state induced by hypoxia.