Adriana E. Rosato, Ph.D.
Postdoctoral Fellowship, Microbiology and Infectious Diseases, University of Southern California/Children's Hospital Los Angeles, Los Angeles, CA
Postdoctoral Fellowship, Microbiology and Infectious Diseases, Virginia Commonwealth University, Richmond, VA
After receiving her Ph.D. in microbiology from the University of Paris, XI, in Paris, France, Dr. Rosato completed a postdoctoral fellowship in microbiology and infectious diseases at the University of Southern California and Children’s Hospital Los Angeles. She then completed a second fellowship at Virginia Commonwealth University in Richmond, VA where she was the recipient of a prestigious National Research Service Award from the National Institutes of Health. Dr. Rosato remained at Virginia Commonwealth University after her postdoctoral training and became an assistant professor in the Department of Internal Medicine, Division of Infectious Diseases. She earned numerous honors while there, including the Faculty Award for Distinguished Research, and three faculty awards from the American Society of Microbiology for her mentoring of minority trainees. Dr. Rosato joined the Center for Molecular and Translational Human Infectious Diseases Research at The Methodist Hospital Research Institute in 2010.
Dr. Rosato's laboratory 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 healthcare 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 laboratory uses molecular biology techniques to understand the genetic basis of antimicrobial resistance and resistance gene spread among S. aureus cells. Preliminary studies from the laboratory 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 a 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 laboratory are investigating 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.
Methicillin-resistant Staphylococcus aureus (MRSA), mecA, penicillin-binding protein 2a (PBP2a), drug resistance, molecular biology
Plata KB, Riosa S, Singh CR, Rosato RR, Rosato AE. Targeting of PBP1 by ß-lactams Determines recA/SOS Response Activation in Heterogeneous MRSA Clinical Strains. PLoS One. 2013 Apr 23;8(4):e61083. PMID: 23637786
Mehta S, Singh C, Plata KB, Chanda PK, Paul A, Riosa S, Rosato RR, Rosato AE. ß-lactams increase the antibacterial activity of daptomycin against clinical MRSA strains and prevent selection of DAP-resistant derivatives. Antimicrob Agents Chemother. 2012 Dec;56(12):6192-200.
Bearman GM, Rosato A, Elam K, Sanogo K, Stevens MP, Sessler CN, Wenzel RP. A crossover trial of antimicrobial scrubs to reduce methicillin-resistant Staphylococcus aureus burden on healthcare worker apparel. Infect Control Hosp Epidemiol. 2012 Mar;33(3):268-75.
Ciustea M, Mootien S, Rosato AE, Perez O, Cirillo P, Yeung KR, Ledizet M, Cynamon MH, Aristoff PA, Koski RA, Kaplan PA, Anthony KG. Thiadiazolidinones: a new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus. Biochem Pharmacol. 2012 Feb1;83(3):368-77.
Mehta S, Cuirolo AX, Plata KB, Riosa S, Silverman JA, Rubio A, Rosato RR, Rosato AE. VraSR two-component regulatory system contributes to mprF-mediated decreased susceptibility to daptomycin in in vivo-selected clinical strains of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2012 Jan;56(1):92-102.
Plata KB, Rosato RR, Rosato AE. Fate of Mutation Rate Depends on agr Locus Expression during Oxacillin-Mediated Heterogeneous-Homogeneous Selection in Methicillin-Resistant Staphylococcus aureus Clinical Strains. Antimicrob Agents Chemother. 2011 Jul;55(7):3176-86.
Bearman G, Rosato AE, Duane TM, Elam K, Sanogo K, Haner C, Kazlova V, Edmond MB. Trial of universal gloving with emollient-impregnated gloves to promote skin health and prevent the transmission of multidrug-resistant organisms in a surgical intensive care unit. Infect Control Hosp Epidemiol. 2010 May;31(5):491-7.
Bearman GM, Rosato AE, Assanasen S, Kleiner EA, Elam K, Haner C, Wenzel RP. Nasal carriage of inducible dormant and community-associated methicillin-resistant Staphylococcus aureus in an ambulatory population of predominantly university students. Int J Infect Dis. 2010 Jan 27.
Plata K, Rosato AE, Wegrzyn G. Staphylococcus aureus as an infectious agent: overview of biochemistry and molecular genetics of its pathogenicity. Acta Biochim Pol. 2009;56(4):597-612.
Higgins PG, Rosato AE, Seifert H, Archer GL, Wisplinghoff H. Differential expression of ccrA in methicillin-resistant Staphylococcus aureus strains carrying staphylococcal cassette chromosome mec type II and IVa elements. Antimicrob Agents Chemother. 2009 Oct;53(10):4556-8.
Cuirolo A, Plata K, Rosato AE. Development of homogeneous expression of resistance in methicillin-resistant Staphylococcus aureus clinical strains is functionally associated with a beta-lactam-mediated SOS response. J Antimicrob Chemother. 2009 Jul;64(1):37-45.
Forbes BA, Bombicino K, Plata K, Cuirolo A, Webber D, Bender CL, Rosato AE. Unusual form of oxacillin resistance in methicillin-resistant Staphylococcus aureus clinical strains. Diagn Microbiol Infect Dis. 2008 Aug;61(4):387-95.
Goldstein F, Perutka J, Cuirolo A, Plata K, Faccone D, Morris J, Sournia A, Kitzis MD, Ly A, Archer G, Rosato AE. Identification and phenotypic characterization of a beta-lactam-dependent, methicillin-resistant Staphylococcus aureus strain. Antimicrob Agents Chemother. 2007 Jul;51(7):2514-22.