The World Health Organization has warned that antimicrobial resistance threatens to return us to a post-antibiotic era, in which routine infections may once again become difficult or impossible to treat. Meeting this challenge will require not only the discovery of new antibiotics, but also new strategies for using existing drugs more effectively.

Our lab focuses on the latter goal: understanding how bacterial physiology, metabolism, population structure, and ecological interactions shape antibiotic efficacy and the evolution of resistance. We study why antibiotics sometimes fail at high bacterial densities, how metabolic state alters drug susceptibility, how plasmids and horizontal gene transfer change treatment outcomes, and how dosing strategies can be designed to preserve the usefulness of tried-and-tested antibiotics. By combining systems biology, microbial ecology, and quantitative experiments, we aim to identify treatment principles that extend the effective lifespan of existing antimicrobial therapies.

Kalifa Torjeman, A.R., Singh, K.,  Ibrahim, P.,  Moulder, T., Nuha, N., Gumirov, J., Rakela, T., Mcmenamin, D.P., Winget, D., White, T., Pipalva, A., Lopatkin, A.J., and Smith, R.P. A biphasic metabolic–growth trade-off governs β-lactam inoculum effects. bioRiv

Ahmad, M.,  Aduru, S.V.,   Smith, R.P.,  Zhao, Z., and Lopatkin, A.J. (2025) The role of bacterial metabolism in antimicrobial resistance. Nature Microbiology Reviews. 1-16.

Hernandez, D. M.,  Marzouk, M., Cole, M., Fortoul, M. C., Kethireddy, S. R., Contractor, R., ... & Smith, R. P. (2024). Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and -lactam antibiotics. Microbiology Spectrum. e01895-24.

Aduru, S.V.,  Szenkiel, K.,  Rahman, A.,  Ahmad, M., Fabozzi, M., Smith, R.P., and Lopatkin A.J. (2024). Sub-inhibitory antibiotic treatment selects for enhanced metabolic efficiency. Microbiology Spectrum. e03241-23.

Palomino, A., Gewurz, D., DeVine, L., Zajmi, U., Moralez, J., Abu-Rumman, F., Smith, R.P. and Lopatkin, A.J., (2023). Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment. The ISME Journal, 17(1), pp.151-162.

Diaz-Tang, G., Meneses, E.M., Patel, K., Mirkin, S., García-Diéguez, L., Pajon, C., Barraza, I., Patel, V., Ghali, H., Tracey, A.P., Blanar, C.A., Lopatking, A.J., and Smith, R.P. (2022) Growth productivity as a determinant of the inoculum effect for bactericidal antibiotics. Science Advances, 8(50), p.eadd0924.

Smith, R.P., Doiron, A.,  Muzquiz, R.,  Fortoul , M.C. Haas, M. Abraham, T. Quinn, R.  Barraza, I.  Chowdhury, K and Nemzer, L.R. (2019) The public and private benefit of an impure public good determines the sensitivity of bacteria to population collapse in a snowdrift game. Environmental Microbiology. doi: 10.1111/1462‐2920.14796

Lopatkin, A. J., Huang, S., Smith, R. P., Srimani, J. K., Sysoeva, T. A., Bewick, S., ... & You, L. (2016). Antibiotics as a selective driver for conjugation dynamics. Nature Microbiology, 1,   16044.

Tan, Cheemeng, Smith. R.P., Tsai, M, Schwartz, R.,  and You, L. "Phenotypic signatures arising from unbalanced bacterial growth." PLoS Comput Biol 10, no. 8 (2014): e1003751.

Tan, C., Smith, R.P., Riccione, K., Pai, Anada, Prasada, S., Kuehn, M., and You, L. (2012) The inoculum effect and band-pass bacterial response to periodic antibiotic treatment. Molecular Systems Biology. 8:617.