title: A whole genome bioinformatic approach to determine potential latent phase specific targets in Mycobacterium tuberculosis.
abstract: Current Tuberculosis treatment is long and expensive, faces the increasing burden of MDR/XDR strains and lack of effective treatment against latent form, resulting in an urgent need of new anti-TB drugs. Key to TB biology is its capacity to fight the host's RNOS mediated attack. RNOS are known to display a concentration dependent mycobactericidal activity, which leads to the following hypothesis "if we know which proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resulting in a synergistic bactericidal effect". Based on this idea, we performed an Mtb metabolic network whole proteome analysis of potential RNOS sensitive and relevant targets which includes target druggability and essentiality criteria. Our results, available at http://tuberq.proteinq.com.ar yield new potential TB targets, like I3PS, while also providing and updated view of previous proposals becoming an important tool for researchers looking for new ways of killing TB.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina.
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Defelipe
authors.affiliation: Plataforma de Bioinformática Argentina, Instituto de Cálculo, Pabellón 2, Ciudad Universitaria, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina.
authors.forename: Dario Fernández
authors.initials: DF
authors.lastname: Do Porto
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Bahia, Brazil; Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil.
authors.forename: Pablo Ivan
authors.initials: PI
authors.lastname: Pereira Ramos
authors.affiliation: Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil.
authors.forename: Marisa Fabiana
authors.initials: MF
authors.lastname: Nicolás
authors.affiliation: Plataforma de Bioinformática Argentina, Instituto de Cálculo, Pabellón 2, Ciudad Universitaria, Facultad de Ciencias Exactas y Naturales, UBA, Buenos Aires, Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Sosa
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina.
authors.forename: Leandro
authors.initials: L
authors.lastname: Radusky
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina.
authors.forename: Esteban
authors.initials: E
authors.lastname: Lanzarotti
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina. Electronic address: adrian@qi.fcen.uba.ar.
authors.forename: Adrián G
authors.initials: AG
authors.lastname: Turjanski
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina. Electronic address: marcelo@qi.fcen.uba.ar.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Marti
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D055808:Drug Discovery / Q000379:methods*; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D055106:Genome-Wide Association Study; D054884:Host-Pathogen Interactions; D006801:Humans; D055985:Latent Tuberculosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D008810:Mice, Inbred C57BL; D050296:Microbial Viability; D058990:Molecular Targeted Therapy; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species
keywords: Latent phase; Mycobacterium tuberculosis; Reactive oxygen and nitrogen species (RNOS); Structural bioinformatics