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.
Nicolaou, K.C., Hale, C.R.H., Nilewski, C., Ioannidou, H.A., ElMarrouni, A., Nilewski, L.G., Beabout, K., Wang, T.T., and Shamoo, Y. (2014). "Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation." Journal of the American Chemical Society.
Davlieva, M., Donarski, J., Wang, J., Shamoo, Y., and Nikonowicz, E.P. “Structure Analysis of free and bound states of an RNA Aptamer Against Ribosomal Protein S8 from Bacillus anthracis” (in press for Nucl. Acids Res)
Reyes, J., Panesso, D., Tran, T.T., Mishra, N., Latorre, M., Cruz, M.R., Munita, J.M., Gonzalez, M., Singh, K.V., Yeaman, |M., Murray, B.E., Yeaman, M., Shamoo, Y., Garsin, D., Bayer, A.S. and Arias, C.A. “Restoring Susceptibility of Drug Resistant Enterococcus faecalis to Antimicrobial Peptides by Interfering with Membrane Adaptation” in press.
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).