A whole genome bioinformatic approach to determine potential latent phase specific targets in Mycobacterium tuberculosis

• Published in: Tuberculosis (Edinburgh, Scotland) Scotland), 2016-03, Vol.97, p.181-192
• Main Authors: Defelipe, Lucas A, Do Porto, Dario Fernández, Pereira Ramos, Pablo Ivan, Nicolás, Marisa Fabiana, Sosa, Ezequiel, Radusky, Leandro, Lanzarotti, Esteban, Turjanski, Adrián G, Marti, Marcelo A
• Format: Article
• Language: English
• Subjects: Animals; Antitubercular Agents - therapeutic use; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Computational Biology; Databases, Genetic; Drug Discovery - methods; Gene Expression Profiling; Genome, Bacterial; Genome-Wide Association Study; Host-Pathogen Interactions; Humans; Infectious Disease; Latent phase; Latent Tuberculosis - drug therapy; Latent Tuberculosis - metabolism; Latent Tuberculosis - microbiology; Mice, Inbred C57BL; Microbial Viability; Molecular Targeted Therapy; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - metabolism; Mycobacterium tuberculosis - pathogenicity; Oligonucleotide Array Sequence Analysis; Protein Interaction Maps; Pulmonary/Respiratory; Reactive Nitrogen Species - metabolism; Reactive oxygen and nitrogen species (RNOS); Reactive Oxygen Species - metabolism; Signal Transduction; Structural bioinformatics
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2015.11.009

Summary 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.