Choon Kim

Research Interests

Methicillin-resistant Staphylococcus aureus (MRSA) is a nefarious human pathogen. It causes both hospital-acquired (HA-MRSA) and community-acquired (CA-MRSA) infections. MRSA kills approximately 11,000 individuals annually in the United States alone. About 80% of MRSA bacteria harbor a bla operon that consists of two regulatory genes, blaR1 and blaI, and a structural gene blaZ encoding a class A β-lactamase (BlaZ), a resistant determinant for β-lactam antibiotics. Dr. Kim recently identified for the first time that the staphylococcal BlaZ exists in two forms, one phosphorylated and another not phosphorylated. A remarkable feature of this discovery is that when the protein is phosphorylated, it is sequestered exclusively to the bacterial membrane by lipidation, whereas the non-phosphorylated form is excreted to the milieu. An intriguing observation pointed to the potential involvement of BlaZ in staphylococcal virulence. When the blaZ was removed from MRSA, it exhibited an increase of opsonophagocytic killing by neutrophil cells as well as a decrease in deposition of the complementary protein C3b.

Dr. Kim’s research focuses on the elucidation of the pathways that inhibition of phosphorylation of BlaZ would target for release from the S. aureus surface, leading to its loss as a virulence factor for the bacterium. We expect that our identification of the kinase(s) phosphorylating BlaZ will make it a target for inhibition that converts virulent strains to avirulent ones.

Selected Publications

• El-Araby, A. M.; Jiménez-Faraco, E.; Feltzer, R.; Martin-Garcia, J. M.; Karri, B. R.; Ramachandran, B.; Kim, C.; Fisher, J. F.; Hermoso, J. A. and Mobashery, S. "Catalytic Process of Anhydro-N-Acetylmuramic Acid Kinase from Pseudomonas Aeruginosa" 2023 Journal of Biological Chemistry, 299 (10), 105198. DOI: 10.1016/j.jbc.2023.105198.
• Avila-Cobian, L. F.; Hoshino, H.; Horsman, M. E.; Nguyen, V. T.; Qian, Y. Y.; Feltzer, R.; Kim, C.; Hu, D. D.; Champion, M. M.; Fisher, J. F. and Mobashery, S. "Amber-Codon Suppression for Spatial Localization and in Vivo Photoaffinity Capture of the Interactome of the Pseudomonas Aeruginosa Rare Lipoprotein A Lytic Transglycosylase" 2023 Protein Science, 32 (10), e4781. DOI: 10.1002/pro.4781.
• Kim, C.; Lee, M.; Birhanu, B. T.; Hesek, D.; Chang, M. and Mobashery, S. "Synthesis of Muramyl-Δ-Lactam in Spore Peptidoglycan of Clostridioides Difficile" 2023 ChemBioChem, 24 (11), e202300282. DOI: 10.1002/cbic.202300282.
• Janardhanan, J.; Kim, C.; Qian, Y. Y.; Yang, J. D.; Meisel, J. E.; Ding, D. R.; Speri, E.; Schroeder, V. A.; Wolter, W. R.; Oliver, A. G.; Mobashery, S. and Chang, M. Y. "A Dual-Action Antibiotic that Kills Clostridioides Difficile Vegetative Cells and Inhibits Spore Germination" 2023 Proceedings of the National Academy of Sciences of the United States of America, 120 (20), e2304110120. DOI: 10.1073/pnas.2304110120.
• El-Araby, A. M.; Feltzer, R.; Kim, C. and Mobashery, S. "Application of 2D-ITC to the Elucidation of the Enzymatic Mechanism of N-Acetylmuramic Acid/N-Acetylglucosamine Kinase (AmgK) from Pseudomonas Aeruginosa" 2023 Biochemistry, 62 (8), pp.1337-1341. DOI: 10.1021/acs.biochem.3c00090.
• Kim, C.; Tomoshige, S.; Lee, M.; Zgurskaya, H. I. and Mobashery, S. "Penetration through Outer Membrane and Efflux Potential in Pseudomonas Aeruginosa of Bulgecin A as an Adjuvant to Beta-Lactam Antibiotics" 2023 Antibiotics-Basel, 12 (2), 358. DOI: 10.3390/antibiotics12020358.