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Acetate Kinase (AcK) is Essential for Microbial Growth, and Betel Compounds Potentially Target AcK, PhoP, and MDR Proteins in M. tuberculosis, V. cholerae, and Pathogenic E. coli: An in silico and in vitro Study

Author(s):

Sandeep Tiwari, Debmalya Barh*, M. Imchen, Eswar Rao, Ranjith K. Kumavath, S. Prabu Seenivasan, Arun Kumar Jaiswal, Syed Babar Jamal, Vanaja Kumar, Preetam Ghosh and Vasco Azevedo   Pages 1 - 10 ( 10 )

Abstract:


Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties, suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Keywords:

Infectious disease, Multi-drug resistant, Natural compounds, Piper betel, Tuberculosis

Affiliation:

Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, Kasaragod, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, Kasaragod, Department of Genomic Sciences, School of Biological Sciences, Central University of Kerala, Kasaragod, Department of Bacteriology, National Institute for Research in Tuberculosis (ICMR) (Formerly Tuberculosis Research Centre), Chetpet, Chennai- 600031, PG program in Bioinformatics (LGCM), Institute of Biologic Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, PG program in Bioinformatics (LGCM), Institute of Biologic Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Department of Bacteriology, National Institute for Research in Tuberculosis (ICMR) (Formerly Tuberculosis Research Centre), Chetpet, Chennai- 600031, Department of Computer Science, Virginia Commonwealth University, Richmond, VA-23284, PG program in Bioinformatics (LGCM), Institute of Biologic Sciences, Federal University of Minas Gerais, Belo Horizonte, MG



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