In Silico Subtractive Proteomics Approach for Identification of Potential Drug Targets in Staphylococcus saprophyticus

Abstract

Staphylococcus saprophyticus is a uropathogenic bacteria responsible for acute urinary tract infections (UTIs) mainly in young female patients. Patients suffering from urinary catheterization, pregnant patients, the elderly as well as those with nosocomial UTIs are at greater risk of the colonizing S. saprophyticus infection. The causative factors include benign prostatic hyperplasia, indwelling catheter, neurogenic bladder, pregnancy, and history of frequent UTIs. Recent findings have exhibited that S. saprophyticus is resistant to several antimicrobial agents. Moreover, there is a global concern regarding the increasing level of antimicrobial resistance, which leads to treatment failure and reduced effectiveness of broad-spectrum antimicrobials. Therefore, a novel approach is being utilized to combat resistant microbes since the past few years. Subtractive proteome analysis has been performed with the entire proteome of S. saprophyticus strain American Type Culture Collection (ATCC) 15305 using several bioinformatics servers and software. The proteins that were non-homologous to humans and bacteria were identified for metabolic pathway analysis. Only four cytoplasmic proteins were found possessing the potential of novel drug target candidates. The development of innovative therapeutic agents by targeting the inhibition of any essential proteins may disrupt the metabolic pathways specific to the pathogen, thus causing destruction as well as eradication of the pathogen from a particular host. The identified targets can facilitate in designing novel and potent drugs against S. saprophyticus strain ATCC 15305.

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

“…Three proteins from this study predicted to be involved in the biosynthesis of secondary metabolites are unique to M. genitalium . This is similar to reports from other studies where the proteins associated with this pathway have been described to be essential, non-homologous, and unique to different bacteria pathogens such as Vibrio parahaemolyticus and Staphylococcus saprophyticus [ 23 , 37 ]. Different studies have reported the manipulation of bacterial secondary metabolites pathways and their use as antibiotics, antiviral drugs, and other pharmaceutical drugs [ 38 , 39 , 40 , 41 ].…”

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

“…A total of 10 S. pyogenes essential proteins were involved in these 6 pathways. The results of pathogen-specific pathway identification are consistent with those reported by Goyal et al, Amineni et al, and Shahid et al for A. baumannii, L. interrogans, and S. saprophyticus, respectively [13,55]. Eight out of the ten proteins were found to be involved in H. sapiens and S. pyogenes pathways.…”

“…In comparison with traditional methods, these methods save time, are faster, and are more cost-effective in the drug design process [11]. Using the subtractive proteomics approach, potential targets and vaccine candidates for various pathogenic bacteria have been identified over the last several years [12,13].…”

Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing

“…In silico subtractive approaches, besides being time saving, are cost effective in drug research and development stages [ 15 ]. These approaches were used to identify potential drug targets in many pathogens, including Acinetobacter baumannii , Burkholderia pseudomallei , Mycobacterium avium , Neisseria meningitides , Pseudomonas aeruginosa , Staphylococcus saprophyticus , and Streptococcus pneumoniae [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Similarly, several potential drug targets in H. pylori were also identified [ 12 , 23 , 24 , 25 , 26 ]; however, none of these studies predicted possible drug binding ligands, except for a study that proceeded to druggability analysis [ 27 ].…”