Assistant Research Professor
- 352E Mccourtney Hall
Notre Dame, IN 46556
- +1 574-631-1731
Prospective Graduate Students
Among numerous antibiotics available for treatment of bacterial infections, β-lactams are by far the most widely used drugs. Members of the carbapenem family of β-lactams are used for the treatment of serious, life-threatening infections caused by multi-drug resistant bacteria. The current wide range of β-lactamases capable of degrading carbapenems, also known as carbapenemases, represents the major mechanism of resistance in Gram-negative bacteria. Carbapenemases belong to three molecular classes, A, B, and D. My recent research is focused on studies of class D carbapenemases. The production of these enzymes by the notorious pathogen Acinetobacter baumannii and representatives of the Enterobacteriaceae family of bacteria results in very high mortality rates that can reach 70-80% in some clinics. In collaboration with other researchers, I am involved in studies aimed at elucidation of the structural architecture of class D carbapenemases and the kinetics of their interaction with β-lactams, including novel carbapenemase-stable antibiotics. One of the major goals of this study is to combat infections caused by multi-drug resistant bacterial pathogens.
- Smith, C. A.; Stewart, N. K.; Toth, M.; Quan, P. J.; Buynak, J. D. and Vakulenko, S. B. "The C5 Alpha-Methyl-Substituted Carbapenem NA-1-157 Exhibits Potent Activity Against Klebsiella Spp. Isolates Producing OXA-48-Type Carbapenemases" 2023 ACS Infectious Diseases, 9 (5), pp.1123-1136. DOI: 10.1021/acsinfecdis.3c00059.
- Toth, M.; Stewart, N. K.; Smith, C. A.; Lee, M. J. and Vakulenko, S. B. "The L,D-Transpeptidase Ldt(Ab) from Acinetobacter Baumannii is Poorly Inhibited by Carbapenems and has a Unique Structural Architecture" 2022 ACS Infectious Diseases, 8 (9), pp.1948-1961. DOI: 10.1021/acsinfecdis.2c00321.
- Stewart, N. K.; Toth, M.; Alqurafi, M. A.; Chai, W. R.; Nguyen, T. Q.; Quan, P. J.; Lee, M. J.; Buynak, J. D.; Smith, C. A. and Vakulenko, S. B. "C6 Hydroxymethyl-Substituted Carbapenem MA-1-206 Inhibits the Major Acinetobacter Baumannii Carbapenemase OXA-23 by Impeding Deacylation" 2022 mBio, 13 (3), e00367-22. DOI: 10.1128/mbio.00367-22.
- Toth, M.; Lee, M.; Stewart, N. K. and Vakulenko, S. B. "Effects of Inactivation of D,D-Transpeptidases of Acinetobacter Baumannii on Bacterial Growth and Susceptibility to Beta-Lactam Antibiotics" 2022 Antimicrobial Agents and Chemotherapy, 66 (1), e01729-21. DOI: 10.1128/AAC.01729-21.
- Stewart, N. K.; Toth, M.; Stasyuk, A.; Vakulenko, S. B. and Smith, C. A. "In Crystallo Time-Resolved Interaction of the Clostridioides Difficile CDD-1 Enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D Beta-Lactamases" 2021 ACS Infectious Diseases, 7 (6), pp.1765-1776. DOI: 10.1021/acsinfecdis.1c00094.
- Stewart, N. K.; Toth, M.; Stasyuk, A.; Lee, M.; Smith, C. A. and Vakulenko, S. B. "Inhibition of the Clostridioides Difficile Class D Beta-Lactamase CDD-1 by Avibactam" 2021 ACS Infectious Diseases, 7 (5), pp.1164-1176. DOI: 10.1021/acsinfecdis.0c00714.