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

Abiodun Joseph Fatoba,Matthew Adekunle Adeleke,Moses Okpeku

doi:10.3390/pathogens10080921

Abiodun Joseph Fatoba, Matthew Adekunle Adeleke + Show 1 more

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https://doi.org/10.3390/pathogens10080921

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Journal: Pathogens	Publication Date: Jul 21, 2021
Citations: 19	License type: CC BY 4.0

Affiliation: University of KwaZulu-Natal

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.

Highlights

Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) around the globe and has been implicated in urogenital infections of both men and women [1], which include urethritis [2], cervicitis [3], pelvic inflammatory disease (PID) [4], and preterm birth [5]
Other activities controlled by quorum sensing include antibiotic production and sporulation [45]. This present study showed that the protein translocase subunit that was predicted as a novel drug target is involved in the quorum-sensing metabolic pathway in M. genitalium
The rapid emergence of antimicrobial resistance among Gram-positive bacteria has triggered the need to explore novel drug targets that could assist in designing new antimicrobial agents

Summary

Introduction

Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) around the globe and has been implicated in urogenital infections of both men and women [1], which include urethritis [2], cervicitis [3], pelvic inflammatory disease (PID) [4], and preterm birth [5]. Transmitted Diseases Treatment Guidelines, 2015 by the Centers for Disease Control and Prevention (CDC) [11]. Despite these guidelines, the treatment of M. genitalium infection is still challenging [12]. The treatment of M. genitalium infection is still challenging [12] This pathogen’s lack of cell wall has exempted the use of certain antibiotics such as the beta-lactams (penicillins and cephalosporins) that target cell wall biosynthesis [13]

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