Identification of membrane associated drug targets in Borrelia burgdorferi ZS7- subtractive genomics approach

Abstract

Lyme disease is an infectious disease caused by a spirochete Borrelia burgdorferi ZS7. This spirochete is most often spread by ticks. Single antibiotic therapy is sufficient for containment of the early stage progression of the disease but combinational therapy is more preferred in later stages. Research is in progress for the development of drugs against the pathogen, but till date no vaccines have been developed to effect the late stage infections. There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals. In such condition vaccine becomes the sole alternative for prevention. Therefore effective treatment includes antibiotic combination and combination of antigenic surfaces (for vaccine preparation). Thus, a comprehensive list of drug targets unique to the microorganisms is often necessary. Availability of Borrelia burgdorferi ZS7 proteome has enabled insilico analysis of protein sequences for the identification of drug targets and vaccine targets. In this study, 272 essential proteins were identified out of which 42 proteins were unique to the microorganism. The study identified 15 membrane localized drug targets. Amongst these 15, molecular modeling and structure validation of the five membrane localized drug target proteins could only be achieved because of the low sequence identity of the remaining proteins with RCSB structures. These 3D structures can be further characterized by invitro and invivo studies for the development of novel vaccine epitopes and novel antibiotic therapy against Borrelia burgdorferi.

In Silico Identification of Common Putative Drug Targets among the Pathogens of Bacterial Meningitis

“…Hence, selecting ponA as a potential target for designing inhibitors, would dissolve the structural integrity, flexibility and rigidity of the cell wall, and expose the pathogens to osmolysis in several pathogens. The existing literatures strengthen potentiality of ponA as common drug target against bacterial meningitis [33][34][35][36][37].…”

“…The metabolic pathways are critical for growth and survival of the organisms in extreme conditions. Therefore, proteins from the phosphotransferase, methane metabolism, and bacterial secretion system pathways would be of significant interest as potential drug targets in different bacterial pathogens like Clostridium acetobutylicum [43], Staphylococcus aureus [44], Escherichia coli [45], Clostridium perfringens [46] and Borrelia burgdorferi [37]. Hence, these proteins would become efficient common drug targets against bacterial meningitis.…”

Sexually transmitted diseases putative drug target database: A comprehensive database of putative drug targets of pathogens identified by comparative genomics

“…In the present study, subtractive genomics approach is used to find drug targets in STD pathogens. [1819] About 10435 proteins were studied for their properties to qualify as drug targets. Out them 3955 were metabolically essential for the bacteria under study and 44 were proteins associated with unique pathway so has to act like unique drug targets.…”

Computational Identification of Putative Drug Targets in Malassezia Globosa by Subtractive Genomics and Protein Cluster Network Approach

“…Identification of putative drug targets from annotated metabolic pathways available in KEGG using subtractive genomics/ proteomics has been widely used by several researchers in bacterial pathogens [33][34][35][36][37][38]. Metabolic pathways that are present in both the host and the pathogen are identified as common pathways and those which are present only in infection causing organism but not in the host as unique pathways.…”