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.; 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.
• Avila-Cobian, L. F.; De Benedetti, S.; Kim, C.; Feltzer, R.; Champion, M. M.; Fisher, J. F. and Mobashery, S. "In Vitro Studies of the Protein-Interaction Network of Cell-Wall Lytic Transglycosylase RlpA of Pseudomonas Aeruginosa" 2022 Communications Biology, 5 (1), 1314. DOI: 10.1038/s42003-022-04230-x.
• Choi, Y.; Park, J. S.; Kim, J.; Min, K.; Mahasenan, K.; Kim, C.; Yoon, H. J.; Lim, S.; Cheon, D. H.; Lee, Y.; Ryu, S.; Mobashery, S.; Kim, B. M. and Lee, H. H. "Structure-Based Inhibitor Design for Reshaping Bacterial Morphology" 2022 Communications Biology, 5 (1), 395. DOI: 10.1038/s42003-022-03355-3.
• Martinez-Caballero, S.; Mahasenan, K. V.; Kim, C.; Molina, R.; Feltzer, R.; Lee, M.; Bouley, R.; Hesek, D.; Fisher, J. F.; Munoz, I. G.; Chang, M.; Mobashery, S. and Hermoso, J. A. "Integrative Structural Biology of the Penicillin-Binding Protein-1 from Staphylococcus Aureus, an Essential Component of the Divisome Machinery" 2021 Computational and Structural Biotechnology Journal, 19, pp.5392-5405. DOI: 10.1016/j.csbj.2021.09.018.
• Kim, C.; Mahasenan, K. V.; Bhardwaj, A.; Wiest, O.; Chang, M. and Mobashery, S. "Production of Proteins of the SARS-CoV-2 Proteome for Drug Discovery" 2021 ACS Omega, 6 (30), pp.19983-19994. DOI: 10.1021/acsomega.1c02984.