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Updated: Oct 22, 2025
Novel Sequence Discovery by Subtractive Genomics
Published on: January 25, 2019
Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium
Abiodun Joseph Fatoba1, Moses Okpeku1, Matthew Adekunle Adeleke1
1Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Westville, P/Bag X54001, Durban 4000, South Africa.
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.
Insights
Antimicrobial resistance necessitates new treatments for Mycoplasma genitalium infections. Bioinformatics identified seven essential proteins unique to the pathogen, offering novel drug targets to combat this sexually transmitted infection.
Area of Science:
- Microbiology
- Bioinformatics
- Drug Discovery
Background:
- Mycoplasma genitalium is a sexually transmitted infection causing urethritis, cervicitis, and pelvic inflammatory disease.
- Rising antimicrobial resistance necessitates novel therapeutic targets against M. genitalium.
Purpose of the Study:
- Identify essential, non-homologous proteins in M. genitalium with unique metabolic pathways for drug development.
- Utilize subtractive genomics and bioinformatics to predict novel drug targets.
Main Methods:
- Comparative analysis of M. genitalium and human metabolic pathways to identify pathogen-specific pathways.
- Bioinformatic screening of the M. genitalium proteome for essential, non-homologous cytoplasmic proteins.
- DrugBank database analysis to identify druggable proteins and potential small-molecule drug candidates.
Main Results:
- Identified nine M. genitalium-specific metabolic pathways.
- Discovered 21 essential, non-homologous, cytoplasmic proteins involved in these pathways.
- Selected seven proteins across seven distinct pathways as novel drug targets, with 13 showing druggability against existing drugs.
Conclusions:
- Seven identified proteins represent promising novel drug targets against M. genitalium.
- These targets can guide the development of new drugs to inhibit pathogen-specific pathways and eradicate infection.
