title: The emerging role of gasotransmitters in the pathogenesis of tuberculosis.
abstract: Mycobacterium tuberculosis (Mtb) is a facultative intracellular pathogen and the second largest contributor to global mortality caused by an infectious agent after HIV. In infected host cells, Mtb is faced with a harsh intracellular environment including hypoxia and the release of nitric oxide (NO) and carbon monoxide (CO) by immune cells. Hypoxia, NO and CO induce a state of in vitro dormancy where Mtb senses these gases via the DosS and DosT heme sensor kinase proteins, which in turn induce a set of ∼47 genes, known as the Mtb Dos dormancy regulon. On the contrary, both iNOS and HO-1, which produce NO and CO, respectively, have been shown to be important against mycobacterial disease progression. In this review, we discuss the impact of O2, NO and CO on Mtb physiology and in host responses to Mtb infection as well as the potential role of another major endogenous gas, hydrogen sulfide (H2S), in Mtb pathogenesis.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Chinta
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA; UAB Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Saini
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Glasgow
authors.affiliation: KwaZulu-Natal Research Institute for TB and HIV (KRITH), Durban, South Africa.
authors.forename: James H
authors.initials: JH
authors.lastname: Mazorodze
authors.affiliation: KwaZulu-Natal Research Institute for TB and HIV (KRITH), Durban, South Africa.
authors.forename: Md Aejazur
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: Department of Cardiothoracic Surgery, Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.
authors.forename: Darshan
authors.initials: D
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA; KwaZulu-Natal Research Institute for TB and HIV (KRITH), Durban, South Africa; UAB Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: adrie.steyn@k-rith.org.
authors.forename: Adrie J C
authors.initials: AJ
authors.lastname: Steyn
mesh_terms: D002248:Carbon Monoxide / Q000502:physiology; D064426:Gasotransmitters / Q000502:physiology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000378:metabolism* / Q000382:microbiology
chemical_list: D064426:Gasotransmitters; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002248:Carbon Monoxide; D010100:Oxygen; D006862:Hydrogen Sulfide
keywords: Carbon monoxide; Gasotransmitter; Heme oxygenase-1; Hydrogen sulfide; Hypoxia; Mycobacterium tuberculosis; Nitric oxide; Reactive nitrogen species; Reactive oxygen species