Victor J. Torres, Ph.D.
Associate Professor, Department of Microbiology
Microbiology, and Immunology and Inflammation Graduate Training Programs
Alexandria Life Sciences Center (West Tower)
430 East 29th Street
New York, NY 10016
Lab Rm. 324, Office Rm. 311
Office: (212) 263-9232
Fax: (212) 263-9180
Staphylococcus aureus, MRSA, CA-MRSA, toxin, infection, macrophages, neutrophils, PMN, leukotoxin, gene expression, bacterial pathogenesis, toxin-cell interaction, immune response to infection, regulation of virulence factors, in vivo models of infection, leukocytes, toxin receptors.
Ph.D. in Microbiology and Immunology in 2004,
Vanderbilt University School of Medicine
2005-2008 Vanderbilt University School of Medicine
2008, Assistant professor
2014, Associate professor
1998-2000 NIH-NIGMS: Minority Access to Research Careers (MARC) Scholar.
1999 NSF-Summer Research Training Program (University of Iowa).
1999/2003 Hispanic Scholarship Fellow.
2003 American Society for Microbiology Corporate Partner Travel Grant Award.
2003-2004 NIH-NIGMS: Individual Ruth L. Kirschstein NRSA Predoctoral Fellowship.
2005 Pre-doctoral Sidney P. Colowick Award (Outstanding research achievements in the Department of Microbiology and Immunology; Vanderbilt University School of Medicine).
2006-2008 NIH-NIAID: Individual Ruth L. Kirschstein NRSA Postdoctoral Fellowship.
2006 Collier Award for Outstanding Research at the Gordon Conference on Microbial Toxins and Pathogenicity (Proctor Academy in Andover, NH).
2007 Post-doctoral Sidney P. Colowick Award (Outstanding research achievements in the Department of Microbiology and Immunology; Vanderbilt University School of Medicine).
2007 Best Research Award at the Gordon Conference on Staphylococcal Diseases (Les Diablerets, Switzerland).
2008 Collier Award for Outstanding Research at the Gordon Conference on Microbial Toxins and Pathogenicity (Proctor Academy in Andover,NH).
2008 Levi Watkins Jr., Student Award for Contributions in fostering opportunities for under-represented minorities in education and research (Vanderbilt University School of Medicine).
2009 NIH-NIAID: Research scholar development award (K22).
2009 American Heart Association National Scientist Development Grant.
2014 Burroughs Wellcome Fund: Investigator in the Pathogenesis of Infectious Diseases
RESEARCH INTERESTS: The Torres laboratory is devoted to the study ofStaphylococcus aureus (S. aureus), a Gram-positive bacterium that infects more than 1.2 million individuals per year in US hospitals. S. aureus is responsible for a wide spectrum of diseases, ranging from minor skin and soft tissue infections to more invasive and serious infections such as sepsis, pneumonia, osteomyelitis, and endocarditis. The pathogenesis of S. aureus is linked to the production of an arsenal of virulence factors that promote evasion of the host innate and adaptive immune responses. Among these virulence factors, we are interested in those that are secreted to the extracellular milieu. These "exoproteins" have the potential to interact with host cells to alter the host’s response to infection. Specifically, we are currently studying two types of exoproteins, toxins that directly kill mammalian cells (cytotoxins) and proteins that target and alter immune responses without necessarily affecting the viability of the host cell (immunomodulatory exoproteins). The goals of our laboratory are to: (i) define how S. aureus senses signals encountered during infection to regulate the expression and elaboration of virulence factors that are critical to infection, (ii) elucidate the contribution of cytotoxins to S. aureus virulence using diverse models of infection, and (iii) examine the contribution of innate and adaptive immune responses in controlling S. aureus pathobiology. To accomplish these goals, we employ a multidisciplinary approach that combines techniques from bacteriology, genetics, molecular biology, biochemistry, structural biology, cellular biology, and immunology with ex vivo tissue culture models and in vivo murine models of infection. Our ultimate goal is to provide a platform for the rational design of novel drugs that target virulence factors. Such therapeutics are desperately needed to improve our ability to combat S. aureus, one the most significant microbial threats worldwide.
I. Regulation of S. aureus virulence factors. We are investigating the molecular mechanism by which S. aureus differentially regulates the expression of genes that encode for exoproteins. Most of our efforts have been devoted to studying the transcription factor known as Repressor of Toxins (Rot). Rot is a ~16 kDa conserved helix turn helix (HTH)-type transcriptional regulator that is a member of the staphylococcal accessory regulator family (Sar). Rot is responsible for regulating gene expression in a manner that is linked to bacterial density (quorum). In S. aureus, the accessory gene regulator (Agr) is a two-component quorum sensing system (Agr-TCS) that influences the expression of a large number of virulence factors critical for the pathogenesis of S. aureus. Thus, the Agr-TCS is considered a master regulator. Under low bacterial density the Agr-TCS is mainly inactive and Rot is produced resulting in the repression of a collection of target genes including toxin-coding genes. Once S. aureus reaches quorum, the Agr-TCS is activated resulting in the expression of RNAIII, a regulatory RNA that inhibits the translation of rot mRNA, which ultimately results in derepression of Rot-repressed genes. We are studying the molecular means by which Rot influences both the invasive and evasive potential of S. aureus by differentially regulating the expression of genes that code for exoproteins. Surprisingly, our studies have revealed that Rot, in addition to influencing gene expression on its own, can also work together with other transcriptional regulators to amplify its regulatory network resulting in the activation of a select number of virulence factors. Thus, Rot is a dual regulator that can both activate and repress gene expression. The current goals for this project are to:
1. Define the molecular mechanism of Rot-mediated regulation of virulence factors.
2. Elucidate the impact of the cross talk between Rot and additional regulators on the expression of virulence factors.
3. Define the kinetics of Rot-mediated regulation in vivo during different types of infection.
4. Characterize the contribution of Rot-mediated regulation to S. aureus pathogenesis.
II. S. aureus leukotoxins and their contribution to S. aureus pathogenesis.
A hallmark of S. aureus infections is the formation of abscesses, a battleground where S. aureus combats host leukocytes, a critical line of defense against infection. To avoid killing by immune cells, S. aureus elaborates a collection of bi-component, beta-barrel pore-forming toxins which include LukSF-PV,HlgAB, HlgCB, LukED, and LukAB. These toxins are secreted into the extracellular milieu as water-soluble proteins but upon recognition of target host cells, they bind and insert into the plasma membrane forming transmembrane pores. The pores then induce a variety of cellular responses, which can ultimately lead to cell death. The staphylococcal bi-component leukotoxins exhibit a high degree of amino acid similarity, which has given rise to the perception that these are redundant toxins produced by S. aureus. However, we believe that this presumption is incorrect and that each toxin exhibits both conserved as well as unique properties that facilitate S. aureus avoidance of killing by leukocytes. The current goals for this project are to:
1. Identify cellular factors involved in the tropism of leukotoxins towards different type of leukocytes.
2. Exploit structure-function studies to reveal how these toxins transition from water-soluble monomers to membrane embedded oligomeric pores.
3. Determine the molecular mechanism by which these toxins kill mammalian cells.
4. Define the contribution of toxin-mediated leukocyte injury to S. aureus pathogenesis using in vivo models of infection.
5. Elucidate the role of leukocytes and leukocyte receptors in the protection against S. aureuspathogenesis in vivo.