- Research Assistant Professor, University of Notre Dame
- Research Scientist, University of Notre Dame
- Research Associate, The Rockefeller University
- Postdoctoral Associate, The Rockefeller University
- Ph.D. in Biochemistry, University of Notre Dame
- M.S. in Biology, Chonnam National University, Korea
- B.S. in Genetic Engineering, Chonnam National University, Korea
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. Kimâs 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.
- Speri, E., Kim, C., De Benedetti, S., Qian, Y., Lastochkin, E., Fishovitz, J., Fisher, J. F., Mobashery, S. "Cinnamonitrile adjuvants restore susceptibility to ß-lactams against methicillin-resistant staphylococcus aureus" 2019 ACS Medicinal Chemistry Letters, 10 (8), pp. 1148-1153. DOI:10.1021/acsmedchemlett.9b00169.
- Ceballos, S., Kim, C., Ding, D., Mobashery, S., Chang, M., Torres, C. "Activities of oxadiazole antibacterials against staphylococcus aureus and other gram-positive bacteria" 2018 Antimicrobial Agents and Chemotherapy, 62 (8), e00453-18. DOI: 10.1128/AAC.00453-18
- Kim, C., Hesek, D., Lee, M., Mobashery, S. "Potentiation of the activity of β-lactam antibiotics by farnesol and its derivatives" 2018 Bioorganic and Medicinal Chemistry Letters, 28 (4), pp. 642-645. DOI: 10.1016/j.bmcl.2018.01.028
- Kim, C.K., Milheiriço, C., De Lencastre, H., Tomasza, A. "Antibiotic resistance as a stress response: Recovery of high-level oxacillin resistance in methicillin-resistant Staphylococcus aureus âauxiliaryâ (fem) mutants by induction of the stringent stress response" 2017 Antimicrobial Agents and Chemotherapy, 61 (8), e00313. DOI: 10.1128/AAC.00313-17
- Chung, M., Kim, C.K., Conceição, T., Aires-De-Sousa, M., De Lencastre, H., Tomasz, A. "Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin-susceptible/mecA-positive MRSA strains from Africa" 2016 Journal of Antimicrobial Chemotherapy, 71 (10), dkw209, pp. 2804-2809. DOI: 10.1093/jac/dkw209
- Dordel, J., Kim, C., Chung, M., de la Gándara, M.P., Holden, M.T.J., Parkhill, J., de Lencastre, H., Bentley, S.D., Tomasz, A. "Novel determinants of antibiotic resistance: Identification of mutated Loci in Highly methicillin-resistant subpopulations of methicillin-resistant Staphylococcus aureus" 2014 mBio, 5 (2), e01000-13. DOI: 10.1128/mBio.01000-13.