title: Cholesterol plays a larger role during Mycobacterium tuberculosis in vitro dormancy and reactivation than previously suspected.
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.
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Soto-Ramirez
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Aguilar-Ayala
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Lazaro
authors.initials: L
authors.lastname: Garcia-Morales
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Sofia M
authors.initials: SM
authors.lastname: Rodriguez-Peredo
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Badillo-Lopez
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Rios-Muñiz
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Meza-Segura
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Gelen Y
authors.initials: GY
authors.lastname: Rivera-Morales
authors.affiliation: Laboratorios de Biologicos y Reactivos de Mexico S.A. de C.V., Birmex, Instituto Nacional de Virologia, Prolongacion Manuel Carpio No. 492, Delegación Miguel Hidalgo, 11340, Ciudad de Mexico, Mexico.
authors.forename: Lizbel
authors.initials: L
authors.lastname: Leon-Solis
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Cerna-Cortes
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rivera-Gutierrez
authors.affiliation: Departamento de Inmunobioquimica, Torre de Investigacion, Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes, SSA, Montes Urales 800, Lomas de Chapultepec, Ciudad de Mexico, 11000, Mexico.
authors.forename: Addy C
authors.initials: AC
authors.lastname: Helguera-Repetto
authors.affiliation: Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Prolongacion Carpio y Plan de Ayala s/n, Ciudad de Mexico, 11340, Mexico. Electronic address: jgonzal1212@yahoo.com.mx.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Gonzalez-Y-Merchand
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D055985:Latent Tuberculosis / Q000378:metabolism* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D010100:Oxygen / Q000378:metabolism; D015398:Signal Transduction; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D002784:Cholesterol; D010100:Oxygen
keywords: Cholesterol; Dormancy; Lipids; Mycobacterium tuberculosis; Reactivation