ChoK-ing the Pathogenic Bacteria: Potential of Human Choline Kinase Inhibitors as Antimicrobial Agents
| Autor: | Ling Ling Few, Moad Khalifa, Wei Cun See Too |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Choline kinase 030106 microbiology Review Article medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Membrane Lipids Anti-Infective Agents Drug Resistance Bacterial medicine Choline Kinase Humans Amino Acid Sequence Pathogen Protein Kinase Inhibitors chemistry.chemical_classification General Immunology and Microbiology biology Bacteria Phosphorylcholine Pathogenic bacteria General Medicine Antimicrobial biology.organism_classification 030104 developmental biology Enzyme chemistry Biochemistry Medicine Bacterial outer membrane |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2020 (2020) |
| ISSN: | 2314-6141 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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