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Hugues Ouellet

Faculty RankAssociate Professor
InstitutionUniversity of Texas at El Paso
DepartmentBiological Sciences
AddressDepartment of Biological Sciences
Bioscience bldg, room 5.152
500 W. University
El Paso TX 79968
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    2014 - 20181 SC1 AI116567-01A1 , University of Texas at El Paso

    Collapse Overview 
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    Functional metabolomics and host-Mtb interactions studies
    My research focus is on the role of cholesterol for the pathogenesis of Mycobacterium tuberculosis (Mtb), the cause of approximately 2 million deaths per year worldwide. The long-term goal of this project is to determine whether cholesterol catabolism is a new therapeutic target to treat and control TB. My laboratory is interested in deciphering the cholesterol degradation pathway and identifying the oxidoreductases essential for the initial infection, as well as persistent infection. Isotopically-labeled cholesterol and high resolution LC/MS will be employed as tools to profile cholesterol-derived metabolome of knockout Mtb stains for putative cholesterol catabolic genes. The biochemical characterization of targeted enzymes will help to better understand their role during infection and evaluate their potential as therapeutic targets. The second area of research in our laboratory is to elucidate the roles of the truncated hemoglobins, HbN and HbO, for infectivity and persistence of Mycobacterium tuberculosis. HbN, which is expressed in stationary phase, is a very efficient NO-dioxygenase that was shown to protect cellular respiration against inhibition by nitric oxide in the attenuated M. bovis BCG vaccine strain. On the other hand, HbO, which is constitutively expressed, has a very high for gaseous ligands (O2, CO and NO) and appeared to be toxic when over-expressed. Collectively, these observations suggest that these two hemoglobins play different and important roles in the biology of Mycobacterium tuberculosis.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Aguilera J, Karki CB, Li L, Vazquez Reyes S, Estevao I, Grajeda BI, Zhang Q, Arico CD, Ouellet H, Sun J. Na-Acetylation of the virulence factor EsxA is required for mycobacterial cytosolic translocation and virulence. J Biol Chem. 2020 04 24; 295(17):5785-5794. PMID: 32169899.
      Citations: 12     Fields:    Translation:HumansAnimalsCells
    2. Zhang Q, Wang D, Jiang G, Liu W, Deng Q, Li X, Qian W, Ouellet H, Sun J. EsxA membrane-permeabilizing activity plays a key role in mycobacterial cytosolic translocation and virulence: effects of single-residue mutations at glutamine 5. Sci Rep. 2016 09 07; 6:32618. PMID: 27600772.
      Citations: 23     Fields:    Translation:HumansAnimalsCells
    3. Acosta Y, Zhang Q, Rahaman A, Ouellet H, Xiao C, Sun J, Li C. Imaging cytosolic translocation of Mycobacteria with two-photon fluorescence resonance energy transfer microscopy. Biomed Opt Express. 2014 Nov 01; 5(11):3990-4001. PMID: 25426325.
    4. Ouellet H, Chow ED, Guan S, Cox JS, Burlingame AL, de Montellano PR. Genetic and mass spectrometric tools for elucidating the physiological function(s) of cytochrome P450 enzymes from Mycobacterium tuberculosis. Methods Mol Biol. 2013; 987:79-94. PMID: 23475669.
      Citations: 1     Fields:    Translation:Cells
    5. Sivaramakrishnan S, Ouellet H, Matsumura H, Guan S, Mo?nne-Loccoz P, Burlingame AL, Ortiz de Montellano PR. Proximal ligand electron donation and reactivity of the cytochrome P450 ferric-peroxo anion. J Am Chem Soc. 2012 Apr 18; 134(15):6673-84. PMID: 22444582.
      Citations: 18     Fields:    Translation:Cells
    6. Ouellet H, Johnston JB, de Montellano PR. Cholesterol catabolism as a therapeutic target in Mycobacterium tuberculosis. Trends Microbiol. 2011 Nov; 19(11):530-9. PMID: 21924910.
      Citations: 83     Fields:    Translation:HumansAnimalsCells
    7. Sivaramakrishnan S, Ouellet H, Du J, McLean KJ, Medzihradszky KF, Dawson JH, Munro AW, Ortiz de Montellano PR. A novel intermediate in the reaction of seleno CYP119 with m-chloroperbenzoic acid. Biochemistry. 2011 Apr 12; 50(14):3014-24. PMID: 21381758.
      Citations: 6     Fields:    Translation:Cells
    8. Ouellet H, Kells PM, Ortiz de Montellano PR, Podust LM. Reverse type I inhibitor of Mycobacterium tuberculosis CYP125A1. Bioorg Med Chem Lett. 2011 Jan 01; 21(1):332-7. PMID: 21109436.
      Citations: 14     Fields:    Translation:Cells
    9. Johnston JB, Ouellet H, Ortiz de Montellano PR. Functional redundancy of steroid C26-monooxygenase activity in Mycobacterium tuberculosis revealed by biochemical and genetic analyses. J Biol Chem. 2010 Nov 19; 285(47):36352-60. PMID: 20843794.
      Citations: 49     Fields:    Translation:Cells
    10. Kells PM, Ouellet H, Santos-Aberturas J, Aparicio JF, Podust LM. Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide pimaricin occurs via a hydroperoxoferric intermediate. Chem Biol. 2010 Aug 27; 17(8):841-51. PMID: 20797613.
      Citations: 18     Fields:    Translation:Cells
    11. Johnston JB, Ouellet H, Podust LM, Ortiz de Montellano PR. Structural control of cytochrome P450-catalyzed ?-hydroxylation. Arch Biochem Biophys. 2011 Mar 01; 507(1):86-94. PMID: 20727847.
      Citations: 21     Fields:    Translation:HumansAnimalsCells
    12. Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR. Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol Microbiol. 2010 Aug; 77(3):730-42. PMID: 20545858.
      Citations: 57     Fields:    Translation:Cells
    13. Ouellet H, Johnston JB, Ortiz de Montellano PR. The Mycobacterium tuberculosis cytochrome P450 system. Arch Biochem Biophys. 2010 Jan 01; 493(1):82-95. PMID: 19635450.
      Citations: 41     Fields:    Translation:Cells
    14. Podust LM, Ouellet H, von Kries JP, de Montellano PR. Interaction of Mycobacterium tuberculosis CYP130 with heterocyclic arylamines. J Biol Chem. 2009 Sep 11; 284(37):25211-9. PMID: 19605350.
      Citations: 17     Fields:    Translation:Cells
    15. Ouellet H, Lang J, Couture M, Ortiz de Montellano PR. Reaction of Mycobacterium tuberculosis cytochrome P450 enzymes with nitric oxide. Biochemistry. 2009 Feb 10; 48(5):863-72. PMID: 19146393.
      Citations: 26     Fields:    Translation:AnimalsCells
    16. Li S, Ouellet H, Sherman DH, Podust LM. Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae. J Biol Chem. 2009 Feb 27; 284(9):5723-30. PMID: 19124459.
      Citations: 20     Fields:    Translation:Cells
    17. Jiang Y, Trnka MJ, Medzihradszky KF, Ouellet H, Wang Y, Ortiz de Montellano PR. Covalent heme attachment to the protein in human heme oxygenase-1 with selenocysteine replacing the His25 proximal iron ligand. J Inorg Biochem. 2009 Mar; 103(3):316-25. PMID: 19135260.
      Citations: 4     Fields:    Translation:Humans
    18. Ouellet H, Podust LM, de Montellano PR. Mycobacterium tuberculosis CYP130: crystal structure, biophysical characterization, and interactions with antifungal azole drugs. J Biol Chem. 2008 Feb 22; 283(8):5069-80. PMID: 18089574.
      Citations: 46     Fields:    Translation:Cells
    19. Ouellet H, Milani M, LaBarre M, Bolognesi M, Couture M, Guertin M. The roles of Tyr(CD1) and Trp(G8) in Mycobacterium tuberculosis truncated hemoglobin O in ligand binding and on the heme distal site architecture. Biochemistry. 2007 Oct 16; 46(41):11440-50. PMID: 17887774.
      Citations: 13     Fields:    Translation:Cells
    20. Podust LM, von Kries JP, Eddine AN, Kim Y, Yermalitskaya LV, Kuehne R, Ouellet H, Warrier T, Altek?ster M, Lee JS, Rademann J, Oschkinat H, Kaufmann SH, Waterman MR. Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography. Antimicrob Agents Chemother. 2007 Nov; 51(11):3915-23. PMID: 17846131.
      Citations: 37     Fields:    Translation:Cells
    21. Ouellet H, Ranguelova K, Labarre M, Wittenberg JB, Wittenberg BA, Magliozzo RS, Guertin M. Reaction of Mycobacterium tuberculosis truncated hemoglobin O with hydrogen peroxide: evidence for peroxidatic activity and formation of protein-based radicals. J Biol Chem. 2007 Mar 09; 282(10):7491-503. PMID: 17218317.
      Citations: 12     Fields:    
    22. Milani M, Pesce A, Nardini M, Ouellet H, Ouellet Y, Dewilde S, Bocedi A, Ascenzi P, Guertin M, Moens L, Friedman JM, Wittenberg JB, Bolognesi M. Structural bases for heme binding and diatomic ligand recognition in truncated hemoglobins. J Inorg Biochem. 2005 Jan; 99(1):97-109. PMID: 15598494.
      Citations: 24     Fields:    Translation:AnimalsCells
    23. Dantsker D, Samuni U, Ouellet Y, Wittenberg BA, Wittenberg JB, Milani M, Bolognesi M, Guertin M, Friedman JM. Viscosity-dependent relaxation significantly modulates the kinetics of CO recombination in the truncated hemoglobin TrHbN from Mycobacterium tuberculosis. J Biol Chem. 2004 Sep 10; 279(37):38844-53. PMID: 15234986.
      Citations: 5     Fields:    Translation:Cells
    24. Milani M, Ouellet Y, Ouellet H, Guertin M, Boffi A, Antonini G, Bocedi A, Mattu M, Bolognesi M, Ascenzi P. Cyanide binding to truncated hemoglobins: a crystallographic and kinetic study. Biochemistry. 2004 May 11; 43(18):5213-21. PMID: 15122887.
      Citations: 19     Fields:    Translation:AnimalsCells
    25. Mukai M, Ouellet Y, Ouellet H, Guertin M, Yeh SR. NO binding induced conformational changes in a truncated hemoglobin from Mycobacterium tuberculosis. Biochemistry. 2004 Mar 16; 43(10):2764-70. PMID: 15005611.
      Citations: 9     Fields:    Translation:Cells
    26. Milani M, Pesce A, Ouellet Y, Dewilde S, Friedman J, Ascenzi P, Guertin M, Bolognesi M. Heme-ligand tunneling in group I truncated hemoglobins. J Biol Chem. 2004 May 14; 279(20):21520-5. PMID: 15016811.
      Citations: 30     Fields:    Translation:AnimalsCells
    27. Milani M, Pesce A, Ouellet H, Guertin M, Bolognesi M. Truncated hemoglobins and nitric oxide action. IUBMB Life. 2003 Oct-Nov; 55(10-11):623-7. PMID: 14711009.
      Citations: 15     Fields:    Translation:AnimalsCells
    28. Ouellet H, Juszczak L, Dantsker D, Samuni U, Ouellet YH, Savard PY, Wittenberg JB, Wittenberg BA, Friedman JM, Guertin M. Reactions of Mycobacterium tuberculosis truncated hemoglobin O with ligands reveal a novel ligand-inclusive hydrogen bond network. Biochemistry. 2003 May 20; 42(19):5764-74. PMID: 12741834.
      Citations: 26     Fields:    Translation:Cells
    29. Milani M, Savard PY, Ouellet H, Ascenzi P, Guertin M, Bolognesi M. A TyrCD1/TrpG8 hydrogen bond network and a TyrB10TyrCD1 covalent link shape the heme distal site of Mycobacterium tuberculosis hemoglobin O. Proc Natl Acad Sci U S A. 2003 May 13; 100(10):5766-71. PMID: 12719529.
      Citations: 20     Fields:    Translation:Cells
    30. Ouellet H, Ouellet Y, Richard C, Labarre M, Wittenberg B, Wittenberg J, Guertin M. Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):5902-7. PMID: 11959913.
      Citations: 84     Fields:    Translation:Cells
    31. Mukai M, Savard PY, Ouellet H, Guertin M, Yeh SR. Unique ligand-protein interactions in a new truncated hemoglobin from Mycobacterium tuberculosis. Biochemistry. 2002 Mar 26; 41(12):3897-905. PMID: 11900532.
      Citations: 23     Fields:    Translation:Cells
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