Oregon State University
Provide the following information for the Senior/key personnel and other significant contributors.
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NAME: Bermudez, Luiz E.
eRA COMMONS USER NAME (credential, e.g., agency login): LUIZBERMUDEZ
POSITION TITLE: Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION DEGREE
FIELD OF STUDY
University of Rio de Janeiro, Brazil M.D. 1978 Medicine
University of Rio de Janeiro, Brazil Chief Resident 1979-1980
A. Personal Statement
My laboratory has extensive experience in studying the pathogenesis and treatment of Mycobacterial infections, including M. avium, M. tuberculosis and M. paratuberculosis. We have developed animal models to test several aspects of pathogenesis, and one of the concentration areas is the early events during infection, including the host response. We use new techniques and technology such as genomes, proteome and metabolomics in our studies. The laboratory has also been involved for decades in the development of new therapies for NTM. We have published a large number of papers dealing with the topic of the proposal.
1. Petrofsky M, Bermudez LE. 2005. CD4+ T cells but Not CD8+ or gamma delta+ lymphocytes are required for host protection against Mycobacterium avium infection and dissemination through the intestinal route. Infect Immun. 73(5):2621-2627. PMCID: PMC1087360.
2. Bermudez LE, Parker A, Petrofsky M. 1999. Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour necrosis factor (TNF) and Fas, and involves the activation of caspases. Clin Exp Immunol. 116(1):94-99. PMCID: PMC1905226.
3. Hsu N, Young LS, Bermudez LE. 1995. Response to stimulation with recombinant cytokines and synthesis of cytokines by murine intestinal macrophages infected with Mycobacterium avium complex. Infect Immun. 63(2):528-533. PMCID: PMC173027.
4. Azouaou N, Petrofsky M, Young LS, Bermudez LE. 1997. Mycobacterium avium infection in mice is associated with time-related expression of TH1 and TH2 CD4+ T lymphocyte response. Immunology. 91(3):414-420. PMCID: PMC1364011.
B. Positions and Honors
1980-1984 Assistant Professor of Medicine, National Cancer Institute, Rio de Janeiro, Brazil
1982-1984 Chief, Division of Infectious Diseases and Laboratory for Infectious Diseases Research, Physician Committee of Nosocomial Infections, National Cancer Institute, Rio de Janeiro, Brazil
1982 Visiting Fellow, Division of Infectious Diseases, University of Tennessee, Memphis
1984-1985 Visiting Professor, Post-Doctoral Fellow, UCLA School of Medicine, Division of Infectious Diseases, Los Angeles, CA
1985-2002 Senior Scientist, Kuzell Institute for Arthritis and Infectious Diseases at California Pacific Medical Center Research Institute, San Francisco, CA, Associate Professor, Infectious Diseases and Immunology, Sanford University
1995-2000 Adjunct Professor, Department of Cell and Molecular Biology, San Francisco State University, San Francisco, CA.
2002-2004 Associate Professor, Department of Biomedical Sciences, College of Veterinary Medicine, and Department of Microbiology, College of Science, Oregon State University, Corvallis, Oregon
2003-present Head, Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR
2004-present Professor, Department of Biomedical Sciences, College of Veterinary Medicine, and Department of Microbiology, College of Science, Oregon State University, Corvallis, OR
2008-present Associate Dean for Research and Graduate Education, College of Veterinary Medicine, Oregon State University, Corvallis, OR
2011 Oregon State University Distinguished Professor of Biomedical Sciences
2014-present Director, Comparative Heath Science Graduate Program
Other Experience and Professional Memberships
Member, American Society for Microbiology (held several positions)
Member, Infectious Disease Society of America (held several positions)
Member, American Association for Immunology
Member , ATS (
Infection and Immunity, 1998-2018
Clinical Immunology Reviews, 2004-2009
Editorial Advisory Board, Journal of Infectious Diseases, 2006-2018
Publications Committee, Editorial Board, Journal of Leukocyte Biology, 2009-2012
Editorial Board, Frontiers in Cellular Microbiology, 2010-2012
Pfizer Award for Research Excellence, 2003
Visiting Professor, Johns Hopkins University, 2004
Visiting Professor, Stanford University, Fall, 2005
Visiting Professor, John Hopkins University, 2006
Elected Fellow of the Society for Healthcare Epidemiology of America (SHEA), 2010
Distinguished Professor of Biomedical Science, Oregon State University, 2011.
Distinguished Professor Lecture, University of Guelph, Canada, 2013
Member NIH Bacteriology and Mycology Study Section (BM-1), 1999-2002
NIAAA Study Section, Centers. Chair, 2002-2006
Member, AIDS-Associated Opportunistic Infection and Cancer, NIH Study Section, 2003-2007, Chair 2007-2008
NIH, Chair, Study Section, Biosecurity and Emerging Infections, October, 2008
College of NIH-CSR Reviewers, 2010-2012
Member of Study Section, NIH, Clinical Research and Field Studies on Infectious Diseases, 2010-2016
Member, Study Section Canada, 2003-2006
Member, USDA Study Section, 2013-2017
Member, Cystic Fibrosis Foundation Advisors, 2016-
Board Member of NIAID Board of Scientific Councelors, 2019-2024
C. Contributions to Science
My contributions have been in diverse areas:
Mycobacterial pathogenesis: Over the years my laboratory has advanced the knowledge of earlier interaction between mycobacteria and the host. We discovered that M. avium infection can occur through the intestinal tract and described the molecular mechanisms associated with it. We also have revealed the mechanisms involved in the lung infection, which is a common problem in individuals with chronic lung disease. To increase the understanding of M. avium interaction with the intestinal mucosa, we created an animal model that is used nowadays. Below are some among the published studies.
1. Bermudez LE, Petrofsky M, Kolonoski P, Young LS. 1992. An animal model of Mycobacterium avium complex disseminated infection following colonization of the intestinal tract. J Infect Dis. 165:75-79. PMID: 1727899.
2. Sangari FJ, Goodman J, Bermudez LE. 2000. Mycobacterium avium enters intestinal epithelial cells through the apical membrane but not by the basolateral surface, activates small GTPase Rho, and once within epithelial cells express an invasive phenotype. Cell Microbiol. 2:561-568. doi: 10.1046/j.1462-5822.2000.00080.x.
3. Dam T, Danelishvili L, Wu M, Bermudez LE. 2006. The fadD2 gene is required for efficient Mycobacterium avium invasion of mucosal epithelial cells. J Infect Dis. 193(8):1135-1142. PMID: 16544254.
4. Harriff MJ, Wu M, Wilder C, McNamara M, Kent M, Bermudez LE. 2009. Mycobacterium avium genes MAV 5138 and MAV 3679 are transcriptional regulators that play a role in invasion of epithelial cells, in part by their regulation of Cip A, a putative surface protein interacting with host cell signaling pathways. J. Bacteriol. 191:1132-1142. PMCID: PMC2631991.
We also discovered the Mycobacterium tuberculosis interacts with the lung mucosal epithelium, and described for the first time the mechanism linked to M. tuberculosis crossing the alveolar membrane.
1. Bermudez LE, Goodman J. 1996. Mycobacterium tuberculosis invades and replicates within type II alveolar cells. Infect Immun. 64(4):1400-1406. PMCID: PMC173932.
2. Bermudez LE, Sangari FJ, Kolonoski P, Petrofsky M, Goodman J. 2002. The efficiency of the translocation of Mycobacterium tuberculosis across a bilayer of epithelial and endothelial Cells as a model of the alveolar wall is a consequence of transport within mononuclear phagocytes and invasion of alveolar epithelial cells. Infect Immun. 70:140-146. doi: 10.1128/IAI.70.1.140-146.
Many years ago, my laboratory was the first to demonstrate that Mycobacteria can form biofilm, and to characterize its role in pathogenesis. We identified many of the genes associated with the ability to form biofilms. Biofilms are mainly involved in lung infection, but also in survival in macrophages. Below are some publications on the topic:
1. Carter G, Drummond D, Bermudez LE. 2003. Characterization of biofilm formation by Mycobacterium avium strains. J Med Microbiol. 52:747-752. doi.10.1099/jmm.0.05224-0.
2. Yamazaki Y, Danelishvili L, Wu M, Hidaka E, Katsuyama T, Stang B, Petrofsky M, Bildfell R, Bermudez L. 2006. The ability to form biofilm influences Mycobacterium avium invasion and translocation of bronchial epithelial cells. Cell Microbiol. 8(5):806-814. PMID: 16611229.
3. Rose S, Bermudez LE. 2014. Mycobacterium avium biofilm attenuates human mononuclear phagocyte function by triggering hyper-stimulation and apoptosis during early infection. Infect Immun. 82:405-412. doi: 10.1128/IAI.00820-13. PMCID: PMC3911830.
4. Rose SJ, Bermudez LE. 2016. Identification of bicarbonate as a trigger involved with extracellular DNA export in mycobacterial biofilms. MBio. 7(6). pii:e01597-16. PMID: 27923918.
The work of the laboratory has also discovered many aspects of the macrophage infection with both M. avium and M. tuberculosis. We were the first to demonstrate the importance of TNF-alpha in the host defense against mycobacteria. We also identified many genes associated with M. avium ability to survive in macrophages. We describe many mechanisms used by the bacterium to resist to macrophage killing mechanisms, and how M. avium exit macrophages to infect surrounding phagocytes. We also report that M. avium infects environmental amoeba, and use some of the same strategies used to survive in amoeba to enter and also alter intracellular trafficking in macrophages. The laboratory also has developed a method using X-Ray microscopy to measure single metals in mycobacterial vacuoles in macrophages, and determined some of the influence of these metals in gene regulation inside the phagosome. More recently, we described several novel mechanisms used by M. tuberculosis to prevent macrophage apoptosis.
1. Danelishvili L, Babrak L, Rose S, Everman J, Bermudez LE. 2014. Mycobacterium tuberculosis alters the metalloprotease activity of COP9 signalosome. mBio. 5(4):e01278-14. doi: 10.1128/mBio.01278-14. PMCID: PMC4147862.
2. Danelishvili L, Bermudez LE. 2015. Mycobacterium avium MAV_2941 mimics phosphoinositol-3-kinase to interfere with macrophage phagosome maturation. Microbes Infect. 17(9):628-37, doi: 10.1016/j.micinf.2015.05.005. Epub 2015 Jun 2. PMID: 26043821.
3. Chinison JJ, Danelishvili L, Gupta R, Rose SJ, Babrak LM, Bermudez LE. 2016. Identification of Mybacterium avium subsp. hominissuis secreted proteins using an in vitro system mimicking the phagosomal environment. BMC Microbiol. 16(1):270.
4. Danelishvili L, Rojony R, Parker AL, Rose SJ, Carson KL, Bermudez LE. Mycobacterium avium subsp hominissuis MAV5_06970 promotes rapid apoptosis in secondary-infected macrophages during cell-to-cell spread. Virulence 9: 1267, 2018.
5. Lewis M, Danelishvili L, Rose S, Bermudez LE. MAV_4644 interacts with host cathepsin Z and protects Mycobacterium avium subsp hominissuis from rapid macrophage killing. Microorganisms, 7:149, 2019
Therapy of Mycobacterial Diseases: My laboratory has also tested in experimental models and developed the therapy for M. avium infection used currently to treat patients with the condition. The laboratory has also studied emergency of resistance during therapy. We published over 40 papers in the topic over the years.
1. Babrak L, Danelishvili L, Rose SJ, Bermudez LE. 2015. Microaggregate-associated protein involved in invasion of epithelial cells by Mycobacterium avium subsp. hominissuis. Virulence. 6(7):694-703. doi: 10.1080/21505594.2015.1072676. PMID: 26252358.
2. Everman, J, Ziaie N, Bechler J, Bermudez LE. 2015. Establishing Caenorhabditis elegans as a model for Mycobacterium avium subspecies hominissuis infection and intestinal colonization. Biology Open 2015 4:1330-1335. doi: 10.1242/bio.012260.
3. Rose SJ, Neville ME, Gupta R, Bermudez LE. 2014. Delivery of aerosolized liposomal amikacin as a novel approach for the treatment of nontuberculous mycobacteria in an experimental model of pulmonary infection. PLoS One. 9(9):e108703. doi: 10.1371/journal.pone.0108703. PMID: 25264757.
4. Bermudez LE, Rose SJ, Everman J, Ziaie N. 2018. Establishment of a host-to-host transmission model for Mycobacterium avium subsp. hominissuis using Caenorhabditis elegans and identification of colonization-associated genes, April 2018, Frontiers in Cellular and Infection Microbiology.
5. Blanchard JD, Elias V, Cipolla D, Gonda I, Bermudez LE. 2018. Effective Treatment of Mycobacterium avium subsp. hominissuis and Mycobacterium abscessus Species Infections in Macrophages, Biofilm, and Mice by Using Liposomal Ciprofloxacin. Antimcrob Agents Chemother, 62(10). pii: e00440-18. doi: 10.1128/AAC.00440-18. Print 2018 Oct. PMID: 30012773, PMCID:PMC6153787.[Available 2019-03-24].
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/luiz.bermudez.1/bibliography/44901607/public/?sort=date&direction=ascending.D.
Disclosure: Nothing to disclose
Saturday, October 5
1:45 PM – 3:00 PM