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Vázquez-Torres, Andrés

D.V.M., Ph.D. Associate Professor of Microbiology


Andrés Vázquez-Torres 

 

Andrés Vázquez-Torres, D.V.M., Ph.D., earned his Ph.D. degree from the University of Wisconsin- Madison in 1996 and his D.V.M. degree from the University of Cordoba in Spain in 1998. He completed 5 years of postdoctoral research training at the University of Colorado School of Medicine.

Dr. Vázquez-Torres joined the faculty of the University of Colorado School of Medicine Department of Microbiology in 2001.

Oxygen offers considerable metabolic opportunities to aerobic organisms, but it also imposes substantial challenges to life. The Vazquez-Torres’ lab uses the model organism Salmonella to better understand the molecular mechanisms by which oxygen and its oxidative and nitrosative congeners exert damage to biomolecules. We actively study the adaptations that not only facilitate life in the midst of oxidative and nitrosative stress, but also promote persistence, pathogenicity and antibiotic resistance in clinically important bacteria. Specifically, we are examining how 1) redox signaling regulates bacterial RNA polymerase, 2) reactive species generated in the innate host response cause cytotoxicity, 3) metabolic reprograming protects against oxidative and nitrosative stress, and 4) metabolic adaptations to reactive species cross-protect against antibiotics.

  1. Redox signaling regulates bacterial RNA polymerase. Transcription in Gram-negative bacteria is under the allosteric control that DksA protein and guanosine tetraphosphate nucleotide alarmone exert on the secondary channel of RNA polymerase. Our investigations have revealed a previously unknown layer of transcriptional regulation that depends on redox-based, protein-protein interactions between DksA and the molecular chaperone DnaJ. Tripartite connections between DksA, DnaJ and guanosine tetraphosphate afford a dynamic range of transcriptional responses to various concentrations of reactive species associated with redox signaling or cytotoxicity. The adaptive response mediated by the combined actions of DksA, DnaJ and guanosine tetraphosphate is essential for Salmonella virulence. We are currently investigating the consequences that the competitive binding of DksA and Gre proteins to RNA polymerase has on transcriptional fidelity and DNA integrity.
  2. Reactive species generated in the innate host response cause cytotoxicity. Despite the wide range of biomolecules damaged by reactive species, as yet very few bacterial molecular targets have been identified. Our research has shown that reactive species posttranslationally modify transcriptional factors that are of pivotal importance for the regulation of metabolism and virulence. We have also demonstrated that cytochrome bd of the electron transport chain is a preferred target of nitric oxide. Investigations are in progress to determine how the nitrosylation of terminal cytochromes reprograms metabolism while eliciting antioxidant and antinitrosative defenses, antibiotic resistance, as well as bacterial persistence and pathogenicity.
  3. Metabolic reprograming protects against oxidative and nitrosative stress. Our investigations have demonstrated critical roles for glutathione, periplasmic superoxide dismutase, flavohemoprotein and a unique secretion system in the antioxidant and antinitrosative arsenal of Salmonella. In addition to these protective mechanisms, our recent work has revealed unsuspected roles for metabolic reprograming in the antioxidant and antinitrosative defenses of intracellular Salmonella. We are testing the hypothesis that glycolysis and fermentation protect against oxidative and nitrosative stress by assisting with ATP synthesis, balancing redox, and enabling disulfide bond formation in periplasmic proteins.
  4. Metabolic adaptations to reactive species cross-protect against antibiotics. Despite the strong antimicrobial activity that stems from the nitrosylation of terminal cytochromes of the electron transport chain, diverse bacteria, including Salmonella, Burkholderia and Pseudomonas, use the signaling cascade triggered by the nitrosylation of respiratory cytochromes to become tolerant to a variety of antibiotics of clinical relevance. Our laboratory is elucidating the molecular mechanisms by which nitrosative stress alters nucleotide metabolism and posttranslationally modifies ribosomal proteins, thereby protecting bacteria against antibiotics that inhibit cell wall or protein biosynthesis. In addition to identifying molecular mechanisms of antibiotic tolerance, these investigations will reveal important strategies exploited by human bacterial pathogens to persist in their hosts.
Funding that supports the research in the Vazquez-Torres’ lab:

R01 AI5449 NIAID. (PI, A. Vazquez-Torres). Title: “Analysis of intracellular host defenses in Salmonella pathogenesis.” The major goal of this project is to identify the molecular mechanisms underlying the reactive nitrogen species-mediated repression of Salmonella pathogenicity island-2 transcription. Dates approved: 9/30/03 – 05/30/19.

R01 AI136520 NIAID (PI, A. Vazquez-Torres). Title: “Molecular determinants of oxidative stress in Salmonella pathogenesis.” The major goal of this application is to characterize how central metabolism and the electron transport chain influence the antioxidant defenses of Salmonella. Dates approved: 09/01/18-08/30/23.

I01BX002073 VA-Merit Award. (PI, A. Vazquez-Torres). Title: “Molecular Analysis of Bacterial Adaptive Response to Host Reactive Species.” The goal is to elucidate the molecular mechanisms by which the RNA polymerase-binding regulatory protein DksA regulates bacterial adaptive responses to oxidative and nitrosative stress. Dates approved: 10/01/2013-03/30/2021.

T32 AI052066 Predoctoral Training Grant. (PD, A. Vazquez-Torres). Title: “Molecular Pathogenesis of Infectious Diseases.” The major goals of this pre-doctoral training grant are 1) to educate Ph.D. students in the investigation of fundamental mechanisms by which microbes cause infection, and 2) prepare our graduate students for scientific leadership positions. Dates approved: 09/30/2003-06/30/2023.

Positions:
  • 1987-1989: Intern, Department of Parasitology, Veterinary School, University of Córdoba, Spain.
  • 1989-1990: Visiting Scientist, National Wildlife Health Research Center, Madison, WI.
  • 1990-1991: Visiting Scientist, Department of Animal Health and Biomedical Sciences, and Department of Poultry Sciences, University of Wisconsin-Madison.
  • 1991-1996: Graduate Student, Laboratory of Edward Balish, Ph.D.; Department of Animal Health and Biomedical Sciences; University of Wisconsin-Madison.
  • 1996-2001: Post-Doctoral Fellow, Laboratory of Ferric C. Fang, M.D.; Division of Infectious Diseases; University of Colorado Health Sciences Center.
  • 2001-2008: Assistant Professor, Department of Microbiology; University of Colorado Health Sciences Center.
  • 2005-present: Biomedical Sciences Program Faculty, University of Colorado School of Medicine.
  • 2005-present: Medical Scientist Training Program Faculty, University of Colorado School of Medicine.
  • 2008-2013: Associate Professor with Tenure; Department of Microbiology; University of Colorado School of Medicine.
  • 2010-present: Program Director of the multi-departmental T32 pre-doctoral training grant to study Molecular Pathogenesis of Infectious Diseases.
  • 2012-present: Department of Veterans Affairs and the Department of Defense Medical Research Service Non-Clinician Scientist Intramural Career Program.
  • 2012-present: University of Colorado School of Medicine Molecular Biology Graduate Program.
  • 2013-present: Professor with Tenure, Department of Immunology and Microbiology, University of Colorado School of Medicine.
Honors:
  • Memberships in NIH Study Sections. NIH Bacterial Pathogenesis Study Section (2007-11); NIH T32 Microbiology and Infectious Diseases (MID) (2015-2019); IFNB Merit VA Study Section (2019-2022).
  • Ad hoc Member Study Sections. NIH Bacteriology and Mycology ZRG1 BM-1 (2003); NIH Innate Immunity and Inflammation (III) (2005); NIH Host Interactions with Bacterial Pathogens (2007); Argentinean National Agency for the Promotion of Science and Technology (2001-2005); Wellcome Trust (2001-2004); the European Science Foundation (2009); INFB Merit VA Study Section (2011-2015); NIH T32 Microbiology and Infectious Diseases MID-B (2014); NIH Topics in Bacterial Pathogenesis IDM-B (2015).
  • Editorial Board Member for the journals Infection and Immunity (since 2010); Frontiers in Cellular Microbiology (since 2010); and Scientific Reports (since 2011).
  • Ad hoc Reviewer for the Journals: Antioxidants & Redox Signaling; Am J Physiol; Cell Host Microbe; Cell Microbiol; FEMS Microbiol Letters; Free Radical Biol Med; Immunology; J Clin Microbiol; J Exp Med; J Infect Dis; J Leuk Biol; Microbes Infect; Microbial Pathogenesis; Microbiology; Mol Microbiol; Nature Microbiol; Nitric Oxide; PLoS ONE; PLoS Pathogens; Traffic; Vaccine; Virulence.
  • Society Memberships: American Society of Microbiology; American Academy for the Advancement of Science; American Society for Biochemistry and Molecular Biology.
  • Committee Memberships: Advisory Committee, Boulder 3-D Lab, P01 project (2005); Steering Committee for the Rocky Mountain Research Center of Excellence (2009-2014); Postdoctoral Association Committee, University of Colorado School of Medicine (2008-2009); University of Colorado School of Medicine Faculty Promotions and Tenure Committee (2010-2012); University of Colorado School of Medicine Rules and Governance Committee (2012); External Advisory Committee for the T32 Training Program in Comparative Medicine, College of Veterinary Medicine, Cornell University (2014-present); Vice Chancellor’s Advisory Committee University of Colorado Denver (2014-2018).
Awards:
  • Spanish Ministry of Science and Education Merit Fellowship (1983-1984).
  • F32 Individual National Research Service Award, Department of Health and Human Services (1998-2001).
  • Schweppe Career Development Award from the Schweppe Foundation (2003-2004).
  • Merck Irving S. Sigal Memorial 2004 Award by the American Academy of Microbiology (2004).
  • Burroughs Wellcome Fund Investigators in Pathogenesis of Infectious Diseases Award (2007).
  • Excellence in Teaching Awards presented by the Sophomore Medical Class of the University of Colorado School of Medicine in the academic years 2001-2, 2003-4, 2004-5 and 2010.
  • Excellence in Teaching Award presented by University of Colorado Microbiology Graduate students in 2005.
  • Fellow to the American Academy of Microbiology (2016).

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