Background: 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.
Methods: 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.
Results and Conclusion: 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.