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.
Wang X, Davlieva M, Reyes J, Panesso D, Arias CA, Shamoo Y. A Novel Phosphodiesterase of the GdpP Family Modulates Cyclic di-AMP Levels in Response to Cell Membrane Stress in Daptomycin-Resistant Enterococci. Antimicrob Agents Chemother. 2017 Jan 9. pii: AAC.01422-16. [Epub ahead of print] PMID: 28069645
Montealegre MC, Roh JH, Rae M, Davlieva MG, Singh KV, Shamoo Y, Murray BE. Differential Penicillin-Binding Protein 5 (PBP5) Levels in the Enterococcus faecium Clades with Different Levels of Ampicillin Resistance. Antimicrob Agents Chemother. 2016 Dec 27;61(1). pii: e02034-16. doi: 10.1128/AAC.02034-16. PMID: 27821450
Davlieva M, Tovar-Yanez A, DeBruler K, Leonard PG, Zianni MR, Arias CA, Shamoo Y. An Adaptive Mutation in Enterococcus faecium LiaR Associated with Antimicrobial Peptide Resistance Mimics Phosphorylation and Stabilizes LiaR in an Activated State. J Mol Biol. 2016 Nov 6;428(22):4503-4519. doi: 10.1016/j.jmb.2016.09.016. PMID: 27670715
Tran T.T., Miller W.R., Shamoo Y., Arias CA. Targeting cell membrane adaptation as a novel antimicrobial strategy. Curr Opin Microbiol (2016).
Meyer P.A., et al. Data publication with the structural biology data grid supports live analysis. Nat Commun (2016).