Rosato Lab

Adriana Rosato, PhD
Associate Professor of Pathology and Genomic Medicine
Houston Methodist Academic Institute

Dr. Rosato's lab conducts translational research involving multidrug-resistant bacteria, specifically methicillin-resistant Staphylococcus aureus (MRSA). MRSA continues to be a considerable public health concern. In 2005, the bacteria was responsible for an estimated 94,000 life-threatening infections and almost 19,000 deaths in the United States. More recently, MRSA infections are occurring outside of the traditional hospital settings, appearing in community populations without health care association or identifiable risk factors for infection. Several studies have shown that rates of community-acquired MRSA (CA-MRSA) infection are rising at an alarming pace. As a result, development of new antibiotics and methods to prevent disease transmission in both clinical and community settings have become more important.

Current studies in Dr. Rosato's laboratory aim to identify the molecular genetic causes of drug resistance in MRSA. Data from these investigations could identify new therapeutic targets and aid in the development of novel antimicrobial agents. Her lab uses molecular biology techniques to understand the genetic basis of antimicrobial resistance and resistance gene spread among S. aureus cells. Preliminary studies from the lab have suggested that drug resistance in S. aureus is due to the acquisition of a gene (mecA) that encodes a ß-lactam-insensitive target enzyme, penicillin-binding protein 2a (PBP2a). This enzyme gives the bacterium the ability to cross-link cell walls and grow while the cells' usual cross-linking enzymes are bound and inactivated by exposure to ß-lactam antibiotics. In addition to the increased expression of mecA, exposure of MRSA strains with low-level resistance to ß-lactam antibiotics also illicits an SOS response that leads to an agr genetically controlled, increased mutation rate that helps with the maintenance of cell wall integrity.

Other current studies in the Rosato lab are the underlying molecular mechanisms and signal pathways involved in the development of MRSA strains resistant to daptomycin, a new class of antibiotic that is the clinical mainstay of anti-MRSA therapy. Although daptomycin-resistant S. aureus strains are currently rare, they present a very serious clinical dilemma when encountered because optimal therapies remain undefined.
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