Discovery of Common Putative Drug Targets and Vaccine Candidates for Mycobacterium tuberculosis sp.

Abstract

ABSTRACT
 Mycobacterium tuberculosis is the bacteria that cause tuberculosis (TB), an infection that usually affects the lungs and can be fatal without proper treatment. Combating through available drugs became a difficult task due to drug resistance and lack of appropriate common targets against genetically diverse strains. Since to improve efficacy, the effective targets should be identified and critically assessed. In the study, we aim to predict the potential novel targets against M. tuberculosis strains by employing in silico approach. The complete proteomic datasets of 23 M. tuberculosis strains was comparatively processed by executing R-scripts and eventually predicted 3906 'conserved gene products'. Further, we performed subtractive proteomic approach in search of promising crucial targets. Consequently, eight enzymes and two membrane proteins were prioritized as new therapeutic and vaccine targets respectively which found to have more interactors in network with high-confidence score, druggability and antigenicity. Therefore, outcomes of the study emphasize the importance of new targets may counteract with false-positive/negatives and facilitate appropriate potential targets for a new insight of reliable therapeutic development.
 Key words: Mycobacterium tuberculosis, Multidrug resistance tuberculosis and Extensive drug resistant tuberculosis.

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

“…A list of 22 other virulent MDR and XDR Mtb strains has been reported in the literature ( Supplementary Table 3 ) [ 77 , 78 ]. One membrane vaccine candidate (transmembrane transport protein MmpL4, NP_214964.1) of M. tuberculosis H37Rv was subjected to BLASTp on the NCBI server (E-value <0.0001, query coverage >80%, sequence similarity >90%) against these 22 MDR and XDR Mtb strains.…”

“…To determine whether the selected proteins were preserved in other virulent Mtb strains, we subjected both cytoplasmic and membrane vaccine targets to BLASTp in NCBI, comparing them against 22 virulent Mtb strains documented in the literature [ 77 , 78 ]. The following cut-off parameters were used to screen proteins: an E-value <0.0001, query cover >80%, and similarity >90%.…”

Computational Design of a Multi-Epitope Vaccine Against Porphyromonas gingivalis

“…Homolog proteins (sequence identity >30%) were discarded subsequently. Selecting human homologs could initiate the autoimmune response, negatively impacting the host's healthy cells and tissues (93). Nine cytoplasmic-membrane, two extracellular, one periplasmic, and six outer-membrane proteins were antigenic with molecular weights lower than 110 kDa, and they were not homologous to the human proteome.…”

Recent Insights into the Structure and Function of Mycobacterial Membrane Proteins Facilitated by Cryo-EM

“…Specific inhibitors of Lnt could be designed based on the structural information to study the after-effects of tri-acetylation inhibition in Mtb cell morphology. Apart from such membrane proteins, other relatively smaller proteins like iron import ATP-binding protein, Serine/Threonine-protein kinase, Protoheme IX farnesyltransferase should be targeted for structure determination since these hold great potential as novel drug targets (Nalamolu et al 2019 ).…”