title: ESX-1-induced apoptosis during mycobacterial infection: to be or not to be, that is the question.
abstract: The major Mycobacterium tuberculosis virulence factor ESAT-6 exported by the ESX-1 secretion system has been described as a pro-apoptotic factor by several independent groups in recent years, sustaining a role for apoptosis in M. tuberculosis pathogenesis. This role has been supported by independent studies in which apoptosis has been shown as a hallmark feature in human and mouse lungs infected with virulent strains. Nevertheless, the role of apoptosis during mycobacterial infection is subject to an intense debate. Several works maintain that apoptosis is more evident with attenuated strains, whereas virulent mycobacteria tend to inhibit this process, suggesting that apoptosis induction may be a host mechanism to control infection. In this review, we summarize the evidences that support the involvement of ESX-1-induced apoptosis in virulence, intending to provide a rational treatise for the role of programmed cell death during M. tuberculosis infection.
authors.affiliation: Grupo de Genética de Micobacterias, Department of Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza Zaragoza, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Nacho
authors.initials: N
authors.lastname: Aguiló
authors.affiliation: Grupo de Genética de Micobacterias, Department of Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza Zaragoza, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Dessislava
authors.initials: D
authors.lastname: Marinova
authors.affiliation: Grupo de Genética de Micobacterias, Department of Microbiología, Medicina Preventiva y Salud Pública, Universidad de Zaragoza Zaragoza, Spain ; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martín
authors.affiliation: Cell Immunity in Cancer, Inflammation and Infection group, Biomedical Research Centre of Aragon, Nanoscience Institute of Aragon, Aragon I+D Foundation, IIS Aragon/University of Zaragoza Zaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009164:Mycobacterium Infections / Q000473:pathology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C432969:ESX1 protein, human; C107475:Esx1 protein, mouse; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Mycobacterium tuberculosis; apoptosis; attenuated strains; cell death; necrosis; virulence