Department of Biochemistry & Cell Biology

6100 Main St.

Houston, TX 77005

As antibiotic use has become more widespread over the past several decades, antibiotic resistance has in kind increased at an alarming rate.  Although effort is being devoted to developing new antibiotics, researchers are having difficulty keeping pace with rapidly evolving bacterial populations as newly introduced drugs become obsolete. To better understand how to design or modify antibiotics to retain efficacy against pathogenic bacteria, it is important to first understand evolutionary trajectories leading to antibiotic resistance. 

My project focuses on opportunistic pathogen Enterococcus faecalis.  Although a common commensal gut organism, E. faecalis is frequently associated with multi-drug resistant infections. In our lab, we have demonstrated using in vitro selection on a clinical isolate that E. faecalis has the capacity to evolve resistance to the front-line drug daptomycin, coinciding with recent clinical data.

The goals of my project are to analyze genetic changes leading to daptomycin resistance using comparative whole genome sequencing.  After identifying resistance mutations, we plan to study fitness benefits of individual mutations. We hope to not only better understand evolutionary principles such as adaptive convergence, epistasis and mutational supply in a clinical pathogen, but to establish techniques for predicting clinical mutations using an in vitro system.

PUBLICATIONS

Arias, C., D. Panesso, D. McGrath, X. Qin, M. Mojica, C. Miller, L. Diaz, T. Tran, S. Rincon, E. M. Barbu, J. Reyes, J. Roh, E. Lobos, E. Sodergren, R. Pasqualini, W. Arap, J. Quinn, Y. Shamoo, B. Murray, and G. Weinstock. "Genetic Basis for In Vivo Daptomycin Resistance in Enterococci".The New England Journal of Medicine. (2011)

Miller, C., M. Davlieva, C. Wilson, K .White, R. Couñago, G. Wu, J. Myers, P. Wittung-Stafshede, and Y. Shamoo.  "Experimental Evolution of Adenylate Kinase Reveals Contrasting Strategies toward Protein Thermostability".  Biophys J, 2010.  99(3), 887-896.