Dr. Cesar A. Arias
The University of Texas Health Science Center at Houston
McGovern Medical School
Departments of Internal Medicine-Infectious Diseases & Microbiology and Molecular Genetics
Antibiotic resistance, its clinical impact and the lack of new antibiotics are recognized by the Infectious Diseases Society of America, American Society for Microbiology, Centers for Disease Control, Institute of Medicine, National Institutes of Health, Food and Drugs Administration, and the US Congress as one of our most serious public health problems. Indeed, the World Health Organization has indicated that antibiotic resistance is one of the three biggest threats for public health in the 21st century. Moreover, healthcare-associated (HA) infections caused by multi-drug resistant (MDR) bacteria are estimated to cost >$10 to >$25 billion/year. Among these MDR organisms, enterococci (particularly vancomycin-resistant enterococci [VRE]) and staphylococci (including methicillin-resistant, MRSA) are among the most important nosocomial pathogens. My career has focused on the clinical and molecular aspects of antimicrobial resistance with emphasis on Gram-positive organisms (enterococci and methicillin-resistant Staphylococcus aureus [MRSA]). I have been working in this field for almost 20 years (first paper published in 1993), including my graduate studies and clinical training (residency and fellowship in infectious diseases). I am an infectious diseases clinician and recognize the immense challenges that emergence of antibiotic resistant bacteria has in the management of hospitalized patients. An important focus of my research has been the study of the molecular mechanisms of resistance in both enterococci and staphylococci. The following are the current major ongoing projects in my laboratory:
Molecular mechanisms of daptomycin resistance in enterococci. The goals of this project include: i) Determination of the role of a three component regulatory system (designated liaFSR) in development of daptomycin resistance in vivo, ii) Evaluation of the role of cardiolipin synthase mutations on daptomycin and antimicrobial peptide resistance in enterococci, and iii) In vivo evaluation of combination antibiotic therapies against multi-drug resistant enterococci using a rat endocarditis model.
Acquisition of high-level vancomycin resistance in S. aureus. We have recently described the emergence of a community-associated strain of S. aureus harboring the genes responsible for vancomycin resistance and producing a bloodstream infection in a Brazilian patient. We have performed genomic and phenotypic characterization of this unique strain to understand the molecular events that lead to acquisition of these genes which represent a major public health threat.
Molecular epidemiology of S. aureus and enterococci in South America. We were the first to describe the emergence of a genetic variant of a community-associated MRSA strain in South America and, using genomic sequencing, we are currently gaining insights into the evolution and molecular epidemiology to understand the patterns of dissemination of these bacteria in the region.
Pathogenesis of E. faecium infections. We have identified a megaplasmid in hospital-associated strains of E. faecium that increased virulence in animal models of infection. We are currently elucidating the genes responsible for enhanced virulence on this plasmid.
Novel “anti-adaptation” antibiotics against vancomycin-resistant enterococci. Based on our discoveries on the mechanisms of resistance to antimicrobial peptides in enterococci, we have identified candidate target genes against which small molecules could be developed and used as new antimicrobials. We are currently developing screening strategies to identify such molecules. We expect that these novel compounds may serve as a new class of antimicrobial agents.
Pharmacological approaches to treat multidrug resistant enterococci and staphylococci. We have developed a rat endocarditis model where we could administer antibiotics mimicking human pharmacokinetics. In this model, we are currently testing new therapeutic approaches to treat deep seated enterococcal and staphylococcal infections using combination therapies.
My laboratory has experience in molecular biology techniques (cloning, mutagenesis, MLST, PFGE, RT-PCR, genomic sequencing , and microarray analyses, among others) biofilm assays, fluorescent microscopy, and animal models (peritonitis, urinary tract infections and endocarditis).
We believe that the understanding of the molecular mechanisms of resistance in bacteria has an immense impact in clinical practice. Derived from this knowledge, new diagnostic tests can be developed to identify these organisms (or the genes carried by them) and the clinician can potentially anticipate the response to specific antimicrobial agents (either alone or in combination) and therefore be able to choose wisely the appropriate therapy for a particular condition. We have extensive collaborations with researchers in the US (Washington University at St Louis, Rice University, Houston, Baylor College of Medicine, Houston, TX, The Methodist Research Institute, Houston, TX and Columbia University, NY, among others), Europe (Institute Pasteur, Paris) and South America (Colombia, Chile, Peru, Brazil, Venezuela and Argentina).