Abstract
Novel antimicrobial agents are crucial to combat antibiotic resistance in pathogenic bacteria. Choline kinase (ChoK) in bacteria catalyzes the synthesis of phosphorylcholine, which is subsequently incorporated into the cell wall or outer membrane. In certain species of bacteria, phosphorylcholine is also used to synthesize membrane phosphatidylcholine. Numerous human ChoK inhibitors (ChoKIs) have been synthesized and tested for anticancer properties. Inhibition of S. pneumoniae ChoK by human ChoKIs showed a promising effect by distorting the cell wall and retarded the growth of this pathogen. Comparison of amino acid sequences at the catalytic sites of putative choline kinases from pathogenic bacteria and human enzymes revealed striking sequence conservation that supports the potential application of currently available ChoKIs for inhibiting bacterial enzymes. We also propose the combined use of ChoKIs and nanoparticles for targeted delivery to the pathogen while shielding the human host from any possible side effects of the inhibitors. More research should focus on the verification of putative bacterial ChoK activities and the characterization of ChoKIs with active enzymes. In conclusion, the presence of ChoK in a wide range of pathogenic bacteria and the distinct function of this enzyme has made it an attractive drug target. This review highlighted the possibility of “choking” bacterial ChoKs by using human ChoKIs.
Highlights
Alongside the revolutionary development of antibiotics, many bacteria adapted swiftly and developed resistance to it
Many disease-causing bacteria that have developed antimicrobial resistance (AMR) possess the putative Choline kinase (ChoK) gene with highly conserved amino acid sequences at the catalytic sites. This makes them become plausible targets for currently available ChoK inhibitors (ChoKIs) to add to the arsenal against the threat of infection by antibioticresistant bacteria
While the focus should be on the pathogenic microorganisms especially the ones that have developed AMR, there could be plenty of other applications for ChoKIs such as a relatively safe pesticide for bacteria that damage crops, i.e., agricultural applications
Summary
Alongside the revolutionary development of antibiotics, many bacteria adapted swiftly and developed resistance to it. The key would be the usage of novel drugs designed for eukaryotic cells that have proven to be effective in prokaryotic cells, nanoparticles (NPs), that hold the potential to solve the riddle of AMR, or even a combination between those two solutions to produce a highly effective antibiotic. This might even hinder the ability of the bacteria to develop AMR against it. This significantly indicates the possibility of using eukaryotic ChoKIs on a wide range of pathogenic bacteria especially those that have developed AMR to currently available antibiotics
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