ADAPTATION & ATOMS:
exploring the biophysical origins of molecular evolution
- Methicillin resistant Staphylococcus aureus (MRSA) kills more Americans per year than HIV/AIDS, emphysema, Parkinson’s diseases and homicides COMBINED. (Infectious Disease Society of America)
- Nearly 2 million Americans per year will develop hospital acquired infections (HAIs) (99,000 deaths)
- Sepsis and pneumonia alone kills ~50,000 American per year and costs 21-34 billion dollars mostly due to MDR pathogens
Our interest in molecular evolution is stimulated by the rise in drug resistant pathogens and how understanding the physical basis for adaptation can be used for prediction of resistance and the identification of new targets and strategies for antimicrobial therapies. By combining approaches from biophysics and experimental evolution we are able to identify and characterize intermediates along the mutational pathways of adaptation and then link those intermediates to the overall evolutionary trajectory of the bacterial populations. Adaptive changes in protein sequence and expression impact organismal fitness and, consequently, dictate population dynamics. By combining experimental evolution with molecular biophysics we take a systems level view of adaptation and link it to the molecular mechanism responsible for the resulting evolutionary dynamics.
Miller C, Kong J, Tran TT, Arias CA, Saxer G, Shamoo Y. "Adaptation of Enterococcus faecalis to Daptomycin Reveals an Ordered Progression to Resistance." Antimicrob Agents Chemother. (2013).
Tran TT, Panesso D, Gao H, Roh JH, Munita JM, Reyes J, Diaz L, Lobos EA, Shamoo Y, Mishra NN, Bayer AS, Murray BE, Weinstock GM, Arias CA. "Whole-genome analysis of a daptomycin-susceptible enterococcus faecium strain and its daptomycin-resistant variant arising during therapy." Antimicrob Agents Chemother. (2013).
Walkiewicz, K., Cardenas, A. S. B., Sun, C., Bacorn, C., Saxer, G., & Shamoo, Y. "Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance." Proceedings of the National Academy of Sciences (2012).
Milya Davlieva, Wanna Zhang, Cesar A. Arias and Yousif Shamoo. "Biochemical Characterization of Cardiolipin Synthase Mutations Associated with Daptomycin Resistance in Enterococci." Antimicrob.Agents Chemother. (2012)