Contents lists available at ScienceDirect Gene Reports journal homepage: www.elsevier.com/locate/genrep The methicillin-resistant S. epidermidis strain RP62A genome mining for potential novel drug targets identification Abdul Wadood a,⁎,1 , Mehreen Ghufran a,1 , Asifullah Khan a,1 , Syed Sikander Azam b , Reaz Uddin c , Muhammad Waqas a,1 , Shoaib Saleem a,1 a Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan b National Center for Bioinformatics, Quaid-e-Azam University Islamabad, Islamabad 45320, Pakistan c Dr. Panjwani Center for Molecular Medicine and Drug Research University of Karachi, Karachi, Pakistan ARTICLE INFO Keywords: Subtractive genome analysis S. epidermidis strain RP62A Non-homologous essential proteins Druggability ABSTRACT In unique biofilm-forming methicillin-resistant (MRSE) strains of S. epidermidis have become a serious medical problem due to the emergence of antibiotic resistance strains. There is an essential need to develop novel drug targets to address the new intervention challenge for such multidrug-resistant bacteria. Here we utilized the available genomes and proteome datasets resources of MRSE S. epidermidis RP62A for comparative and sub- tractive genome analyses to identify novel drug targets for future drug discovery approaches. The comparative genome based molecular biology database resources scanning identified 255 proteins as essential human non- homologs targets for epidermidis RP62A that involve in essential metabolic pathways. Among these 12 targets were found to be involved in pathogen unique metabolic pathways. Druggability potential of each of these targets by Drug Bank database further identified 5 proteins as druggable essential proteins. As antimicrobial agents inflict beneficial gut microbiome and the antibiotics causes less agitation in gut flora are considered as best candidates. We pursued additional analysis and screen our lead targets proteins against metagenomes da- tabases holding whole genome sequences of human gut microbiome. The negligible biological similarity with gut microbiota genomes datasets predicting the future implementation of our lead identified proteins as druggable targets for S. epidermidis RP62A that may not affect the essential humans gut microbiota. Based on these evi- dences, we are speculating that the putative druggable proteins addressed in this study are potent enough for their future evaluation as therapeutic targets to combat the S. epidermidis RP62A infections. 1. Introduction The staphylococci bacteria are involved in series of diseases ranging from minor skin to life-threatening infections (Projan and Novick, 1997). The two pathogens of this genus, Staphylococcus aureus and Staphylococcus epidermidis, colonize a large number of human popula- tion. Mostly, S. epidermidis, is highly distributed throughout the cuta- neous ecosystem, while S. aureus is colonizing mainly on mucosal sur- faces. S. epidermidis mainly cause infections that occur by inserting medical devices, such as prosthetic heart valves and joint prostheses (von Eiff et al., 2002). The Staphylococcus epidermidis is considered as nosocomial pathogen causes infections mainly through secretory toxins (Otto, 2009). S. epidermidis only has a minor range of factors that causes virulence. Infections caused by the nosocomial pathogen S. epidermidis frequently develop on implanted medical devices and involve biofilm formation (Klingenberg et al., 2007; Otto, 2004). Due to biofilms for- mation the S. epidermidis infections remain for long time and difficult to treat (Otto, 2009). S. epidermidis is the most common coagulase nega- tive Staphylococcus (CNS) separated from infections which are related to blood stream (Pechorsky et al., 2009). S. epidermidis RP62A is a slime-producing strain isolated during the 1979 to 1980 Memphis, Tennessee, outbreak of intravascular catheter- associated sepsis (Christensen et al., 1982; Christensen et al., 1985). RP62A is capable of accumulated growth and subsequent biofilm for- mation, which contribute to its pathogenicity in foreign-body infections (Hussain et al., 1997). The biofilm-producing S. epidermidis strain, i.e., RP62A contain intercellular adhesion locus (icaABCD) and the cell wall associated biofilm protein (Bap) or Bap homologous protein (Bhp) as http://dx.doi.org/10.1016/j.genrep.2017.06.002 Received 2 April 2017; Received in revised form 28 May 2017; Accepted 8 June 2017 ⁎ Corresponding author. 1 Web: www.awkum.edu.pk. E-mail address: awadood@awkum.edu.pk (A. Wadood). Abbreviations: MRSE, Methicillin resistant Staphylococcus epidermidis.; NCBI, National Center for Biotechnology Information.; H. sapiens, Homo sapiens.; DEG, Database of Essential Genes.; KEGG, Kyoto Encyclopedia of Genes and Genomes.; PDB, Protein Data Bank. Gene Reports 8 (2017) 88–93 Available online 15 June 2017 2452-0144/ © 2017 Published by Elsevier Inc. MARK