Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium

Abstract

Mycoplasma genitalium infection is a sexually transmitted infection that causes urethritis, cervicitis, and pelvic inflammatory disease (PID) in men and women. The global rise in antimicrobial resistance against recommended antibiotics for the treatment of M. genitalium infection has triggered the need to explore novel drug targets against this pathogen. The application of a bioinformatics approach through subtractive genomics has proven highly instrumental in predicting novel therapeutic targets against a pathogen. This study aimed to identify essential and non-homologous proteins with unique metabolic pathways in the pathogen that could serve as novel drug targets. Based on this, a manual comparison of the metabolic pathways of M. genitalium and the human host was done, generating nine pathogen-specific metabolic pathways. Additionally, the analysis of the whole proteome of M. genitalium using different bioinformatics databases generated 21 essential, non-homologous, and cytoplasmic proteins involved in nine pathogen-specific metabolic pathways. The further screening of these 21 cytoplasmic proteins in the DrugBank database generated 13 druggable proteins, which showed similarity with FDA-approved and experimental small-molecule drugs. A total of seven proteins that are involved in seven different pathogen-specific metabolic pathways were finally selected as novel putative drug targets after further analysis. Therefore, these proposed drug targets could aid in the design of potent drugs that may inhibit the functionality of these pathogen-specific metabolic pathways and, as such, lead to the eradication of this pathogen.

In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against Streptococcus pyogenes

“…Two proteins, i.e., chromosomal replication initiator protein DnaA and two-component response regulator (TCR), were found to be involved in unique metabolic pathway, i.e., a two-component system, and identified as novel drug targets. Several other studies have also reported DnaA [56,57] as a drug target.…”

Subtractive genomics profiling for potential drug targets identification against Moraxella catarrhalis

“…The complete proteome of Moraxella catarrhalis BBH18 was eradicated at 60% threshold using Cluster Database at High Identity with Tolerance i.e. CD-HIT [ 20 , 21 ].The proteins possessing the sequence identity greater than 60% are paralogous to each other. The complete sequences of paralogous i.e.…”

“…Further, the set of proteins retrieved after removal of paralogous were subjected to BLASTp [ 22 ] with the expectation value (i.e. E-value) cut-off of 10 −5 against Homo sapiens proteome [ 21 ]. The BLASTp generated results i.e.…”

“…Later, nonhomologous essential proteins were evaluated using BLASTp against Food and Drug Administration (FDA) approved proteins that served as therapeutic targets and obtained from the DrugBank. The evaluation was performed with E-value cut-off of 10 −5 for the discovery of drug–target-like ability of identified essential proteins for the prioritization of novel and unique therapeutic targets [ 21 ].…”

Proteome Exploration of Legionella pneumophila To Identify Novel Therapeutics: a Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

“…Some receptive membranes are also classified as “anti-target.” They are adrenergic α1a, dopaminergic D2, muscarinic M1, and serotonergic 5-HT2C. A total of 210 human “anti-targets” have been identified in the literature ( 106 ), and the corresponding sequences of these proteins have been obtained from the NCBI protein database. BLASTp analysis was carried out for all nonhomologous, essential “novel drug target” proteins against these “anti-targets,” setting an E value threshold of <0.005, a query length of >30%, and an identity of <30% as parameters.…”