8/24/2023 0 Comments Download pro100 6.41Genomic Target Database (GTD) has been developed for the target identification using subtractive genomics approach (Barh et al., 2009). pallidum strain SS14 along with those of Homo sapiens (Fraser et al., 1998 Matejkova et al., 2008) has made it possible to do comparative analysis of host and pathogen genomes, proteomes as well as metabolomes. have been done using bioinformatics approaches such as subtractive genomics, comparative microbial genomics, and metabolic pathway analyses of genome of the host and pathogens (Anishetty et al., 2005 Barh and Kumar, 2010 Hoseni et al., 2012 Kushwaha and Shakya, 2010 Sharma et al., 2006).Īvailability of complete genome sequences for T. Thus, predictions of novel drug targets in case of a number of other pathogenic bacteria such as Mycobacterium tuberculosis, Neisseria gonorrhoeae, Staphylococcus aureus etc. Designing and virtual screening of inhibitor/drugs against the pathogen-specific unique targets may help in developing potential drugs for fatal STDs including syphilis. These in silico approaches reduce the time as well as the cost of target identification and have made a new paradigm shift in drug discovery research (Barh et al., 2011). Subtractive genomics approaches are meant for screening pathogen-specific targets which are non-human homologous genes/proteins regulating pathogen specific metabolic pathways or biological reactions. Genomics and associated high-throughput technologies provide opportunities for better understanding of infectious disease mechanism, as well as their prevention and treatment. Modern approaches to the understanding of the pathogenesis of syphilis, the development of improved diagnostic tests, and the implementation of decentralized management strategies offer the promise of improving syphilis control (Hook and Peeling, 2004). pallidum (Marra et al., 2006 Mitchell et al., 2006 Stamm, 2010) has significantly hampered the treatment of syphilis. During the past few years, the emergence of an antibiotic-resistant strain of T. People suffering from syphilis are at a two- to five-fold higher risk to develop HIV infection. Other antibiotics, including tetracyclines, macrolides, and cephalosporins, have also been used as an alternative treatment for penicillin-allergic patients (Katz and Klausner, 2008). Generally, antibiotics such as penicillin, erythromycin, and azithromycin are prescribed for treatment of the disease, out of which the intramuscularly administered penicillin G benzathine is the preferred treatment for syphilis, except neurosyphilis (Smith et al., 1956). It is a multistage disease and usually transmitted through contact with active lesions of a sexual partner or from an infected pregnant woman to her fetus. pallidum), is the third most common and slow progressive sexually transmitted disease (STD) found worldwide. S yphilis, caused by a spirochete gram negative bacteria Treponema pallidum subsp pallidum SS14 ( T. Further studies are warranted to evaluate and explore the potential clinical ramifications of these findings in relation to syphilis that has public health importance worldwide. pallidum with D-alanine:D-alanine ligase as a novel target. To the best of our knowledge, this is the first report of a terpenoid as a potential therapeutic molecule against T. A comparison of the inhibitory potential of the best docked readily available natural compound, namely pomiferin (flavonoid) with that of the best docked terpenoid salvicine, revealed that salvicine was a more potent inhibitor than that of pomiferin. Out of five targets analyzed, D-alanine:D-alanine ligase was found to be the most promising target, while terpenoid salvicine was the most potent inhibitor. pallidum targets through molecular modeling approaches. Subsequently the resulting nine terpenoids were docked with five unique T. pallidum, were screened for their drug likeness and ADMET (absorption, distribution, metabolism, and toxicity) properties. One hundred plant-derived terpenoids, as potential therapeutic molecules against T. Metabolic pathway analyses of these essential proteins led to discovery of nineteen proteins distributed among six metabolic pathways unique to T. pallidum and host Homo sapiens resulted in identification of 126 proteins essential for survival and viability of the pathogen. Subtractive genomics analyses of pathogen T. pallidum has led to a search for novel drugs and their targets. Syphilis, a slow progressive and the third most common sexually transmitted disease found worldwide, is caused by a spirochete gram negative bacteria Treponema pallidum.
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