Marta Toth

Research Interests

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.

Selected Publications

• Stewart, N. K.; Toth, M.; Bhattacharya, M.; Smith, C. A. and Vakulenko, S. B. "Evolution of Carbapenemase Activity in the Class C β-Lactamase ADC-1" 2025 MBIO, e00185-25. DOI: 10.1128/mbio.00185-25.
• Toth, M.; Stewart, N. K.; Maggiolo, A. O.; Quan, P. J.; Khan, M.; Buynak, J. D.; Smith, C. A. and Vakulenko, S. B. "Decarboxylation of the Catalytic Lysine Residue by the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the OXA-58 Carbapenemase" 2024 ACS Infectious Diseases, 10 (12), pp.4347–4359. DOI: 10.1021/acsinfecdis.4c00671.
• Stewart, N. K.; Toth, M.; Quan, P. J.; Beer, M.; Buynak, J. D.; Smith, C. A. and Vakulenko, S. B. "Restricted Rotational Flexibility of the C5α-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase" 2024 ACS Infectious Diseases, 10 (4), pp.1232-1249. DOI: 10.1021/acsinfecdis.3c00683.
• 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.