Catherine J. Vilcheze, Ph.D.
- Research Assistant Professor, Department of Microbiology & Immunology
Area of research
- Tuberculosis, antimycobacterial drugs, drug resistance, drug persistence
Phone
Location
- Albert Einstein College of Medicine Jack and Pearl Resnick Campus 1300 Morris Park Avenue 569 Bronx, NY 10461
Research Profiles
Professional Interests
My scientific goals are to find new ways to eradicate Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). My focus has been primarily on establishing the mechanisms of action and resistance of the first-line TB drug isoniazid (INH) in mycobacteria as well as exploring new methods to eliminate persisters generated during INH treatment. INH persisters are genotypically drug-susceptible but phenotypically drug-resistant cells. I serendipitously uncovered that the addition of vitamin C to INH-treated M. tuberculosis cultures eliminated the persister population and allowed for sterilization of i cultures. This work was further substantiated by the discovery that the combination of small thiols and the first-line TB drugs is bactericidal against i leading to sterilization of cultures of drug-susceptible and drug-resistant i strains. This sterilization phenotype is the result of coercing M. tuberculosis into consuming oxygen, which prevents persister formation and produces an oxidative process leading to DNA damage and cell death. The addition of small, non-toxic molecules to TB drug treatment represents an alternative and promising approach to the treatment of drug-resistant TB, a clinically challenging endeavor.
Selected Publications
- Vilchéze C, Jacobs WR Jr. The Isoniazid Paradigm of Killing, Resistance, and Persistence in Mycobacterium tuberculosis. J Mol Biol. 2019 Feb 21;. doi: 10.1016/j.jmb.2019.02.016. PMID: 30797860.
- Vilchéze C, Copeland J, Keiser TL, Weisbrod T, Washington J, Jain P, Malek A, Weinrick B, Jacobs WR Jr. Rational Design of Biosafety Level 2-Approved, Multidrug-Resistant Strains of Mycobacterium tuberculosis through Nutrient Auxotrophy. MBio. 2018 May 29;9(3). pii: e00938-18. doi: 10.1128/mBio.00938-18.
- Vilchéze C, Weinrick B, Leung LW, Jacobs WR Jr. Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their role in virulence. Proc Natl Acad Sci U S A. 2018: 115(7):1599-1604. doi: 10.1073/pnas.1721545115. PMID: 29382761
- Vilchéze C, Kim J, Jacobs WR Jr. Vitamin C potentiates the killing of Mycobacterium tuberculosis by the first-line tuberculosis drugs isoniazid and rifampicin in mice. Antimicrob Agents Chemother. 2018: 62(3) e02165-17. PMID: 29298757
- Vilchéze C, Hartman T, Weinrick B, Jain P, Weisbrod TR, Leung LW, Freundlich JS, Jacobs WR Jr. Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2017;114(17):4495-4500. doi: 10.1073/pnas.1704376114. PMID: 28396391; PMCID: PMC5410800.
- Vilchéze C, Kremer L. Acid-Fast Positive and Acid-Fast Negative Mycobacterium tuberculosis: The Koch Paradox. Microbiol Spectr. 2017;5(2). doi: 10.1128/microbiolspec.TBTB2-0003-2015. PMID: 28337966.
- Vilchéze C, Leung LW, Bittman R, Jacobs WR Jr. Synthesis and biological activity of alkynoic acids derivatives against mycobacteria. Chemistry and physics of lipids. 2016; 194:125-38.
- Vilchéze C, Jacobs WR Jr. Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities. Microbiol Spectr. 2014, 2(4). doi: 10.1128/microbiolspec.MGM2-0014-2013.
- Vilchéze C, Molle V, Carrére-Kremer S, Leiba J, Mourey L, Shenai S, Baronian G, Tufariello J, Hartman T, Veyron-Churlet R, Trivelli X, Tiwari S, Weinrick B, Alland D, Guérardel Y, Jacobs WR Jr, Kremer L. Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis. PLoS Pathog. 2014, 10(5):e1004115.