From Gene to Phenotype: tracking evolution of staphyloccocal drug resistance

From gene to phenotype: tracking evolution of staphyloccocal drug resistance during chemotherapy of a patient - by whole genome sequencing

Speaker: Dr. Alexander Tomasz (Dr. Plutarch Papamarkou Professor)

Affiliation: The Rockefeller University and Adjunct Full Professor at ITQB / UNL

Host: Laboratório Associado

Abstract:

"From gene to phenotype: tracking evolution of staphylococcal drug resistance during chemotherapy of a patient - by whole genome sequencing"

The emergence of rapid global spread of antibiotic resistant clones of human pathogens during the past few decades represents an example of an accelerated evolution on a planetary scale which presents an important challenge to the control of human disease (1).  Recently we were able to obtain a “close-up” of this phenomenon by observing the sequence of mutational changes that accompanied development of Staphylococcal aureus multidrug resistance during the chemotherapy of a single hospitalized patient (2).  The emerging resistant lineage also showed a surprisingly large number and variety of phenotypic alterations.  Besides the excitement of watching evolution in vivo, the project put into sharp focus the fundamental question: how does one go from a gene to a phenotype?    

1. de Lencastre, H.,  D.C. Oliveira and A. Tomasz.  2007.   Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power.   Current Opinion in Microbiol.  10:1-8.
2. Mwangi, M.M., S. W. Wu, Z. Yanjiao, K. Sieradzki, H. de Lencastre, P. Richardson, D. Bruce, E. Rubin, E. Myers, E.D. Siggia and A. Tomasz.  2007.  Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing.  Proc Natl Acad Sci USA. 104:9451-56. 

Short CV:

Alexander Tomasz received a Ph.D. in Biochemistry from Columbia University, New York; joined the Laboratory of Rollin D. Hotchkiss at The Rockefeller University where he rose in rank and is currently Professor and Head of the Laboratory of Microbiology and Infectious Diseases.

 Dr. Tomasz’s Special Functions and Honors include founding the Gordon Research Conference on Bacterial Cell Surfaces; he served as a Chairman of the Board of Scientific Counsellors at NIAID and Member of the Board of Scientific Counsellors, Max Planck Institut fur Molekulare Genetik, Berlin.  He received the first International Hoechst Roussel Award in Chemotherapy, the Selman Waksman Award in Microbiology, an NIH Merit Award, received an Honorary Doctorate from the University of Lisbon, Portugal in 1997 and the award of an Endowed Chair in Infectious Diseases at The Rockefeller University in 1998.

 Dr. Tomasz is an author of over 400 peer reviewed publications and has a primary interest in the microbiology, biochemistry and molecular biology of gram positive pathogens.