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Luiz E. Bermudez
Professional and Research Interests:
The laboratory of Dr. Bermudez is interested in the mechanisms of pathogenesis of intracellular bacteria, with focus on mycobacteria.
Mycobacteria are a common cause of infections in humans and animals. Mycobacterium tuberculosis infects a third of the world population and is responsible for 3 million deaths annually. Mycobacterium avium, an environmental bacterium, commonly causes disseminated disease in patients with Acquired Immunodeficiency Syndrome (AIDS), and pulmonary infection in patients with chronic lung disease, cystic fibrosis, and in elderly women. Mycobacterium avium subsp paratuberculosis is an important agriculture pathogen causing Johne’s disease, a wasting disease in cattle. Mycobacteria also infect fish, and a number of species have been isolated causing disease. The majority of the mycobacterial diseases have, as a hallmark, the formation of granulomas.
Mycobacteria are intracellular pathogens (with a few exceptions), which are able to replicate and survive within macrophages. They evolved pathogenic mechanisms that allow them to enter in macrophages (phagocytosis) by non-traditional pathways, inhibit acidification of the intracellular vacuole where they live, and prevent fusion of this vacuole with the bactericidal enzymes-loaded lysosomes. Our laboratory is interested in the mechanisms of uptake of mycobacteria by macrophages, both the first macrophage encountered by the bacterium, as well as the subsequent ones (as part of the dissemination process). We are also interested in mycobacterial genes involved in the early events in the infection of macrophages, as well as in the spreading of the infection and an experimental model to study it.
The great majority of the pathogens need sophisticated means to cross the mucosal barrier before being able to cause infection. Mycobacteria are not an exception. M. tuberculosis crosses the respiratory mucosa; M. avium crosses both the respiratory and the intestinal mucosas, and M. paratuberculosis invades the intestinal mucosa in cattle. It is clear now that all these pathogens have evolved mechanisms to subvert the host pathways and are able to infect cells. Because mucosal epithelial cells are not phagocytic cells, the pathogen needs to manipulate the host cell (signal pathways and trafficking) to be able to enter and cross it. Our laboratory studies how the three mycobacteria cited above can cross the epithelial mucosa of the host. We use cell biology and molecular biology techniques for insights into how mycobacteria can invade the host mucosa, use signal transduction pathways to advantage, and surpass the host immune response.
Recently, we began to work on the mechanism of pathogenesis of two zoonoses, i.e., brucellosis and tularenia (Brucella abortus and Francisella tularensis). Our studies aim to identify how those pathogens interact with host innate immune response.
Trainees in the laboratory are exposed to a number of techniques in cell and molecular biology, several models of bacterial infection, and bioinformatics.
1. Zhao M, Gilbert K, Danelishvili L, Bermudez LE. Identification of Mycobacterium avium prophages with a role in biofilm formation. Submitted.
2. Danelishvili L, McNamara M, Tripathi S, Bermudez LE. Mycobacterium avium MAV_2941 interacts with the adaptor protein AP3B1 and competes for PI3K altering phagosome maturation in macrophages. Submitted.
3. Rose S, Bermudez LE. Mycobacterium avium triggers hyperstimulation and apoptosis of human mononuclear phagocytes. Submitted.
4. Rose S, Neville M E, Gupta R., Bermudez LE. Evaluation of aerosol delivered liposome-encapsulated amikacin for the treatment of non-tuberculosis mycobacteria in vitro and in vivo. Submitted.
Chacon O, Bermudez LE, Zinniel DK, Chahal HK, Fenton RJ, Feng Z, Hanford K, Adams GL, Barletta RG. 2009. Impairment of D-alanine biosynthesis in Mycobacterium smegmatis determines decreased intracellular survival in human macrophages.. Microbiology (Reading, England). 155(Pt 5):1440-50.
Harriff MJ, Danelishvili L, Wu M, Wilder C, McNamara M, Kent ML, 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 CipA, a putative surface protein interacting with host cell signaling pathways.. Journal of bacteriology. 191(4):1132-42.
Bermudez LE, Motamedi N, Kolonoski P, Chee C, Baimukanova G, Bildfell RJ, Wang G, Phan LT, Lowell YS. 2008. The efficacy of clarithromycin and the bicyclolide EDP-420 against Mycobacterium avium in a mouse model of pulmonary infection.. The Journal of infectious diseases. 197(11):1506-10.
Alonso-Hearn M, Patel D, Danelishvili L, Meunier-Goddik L, Bermudez LE. 2008. The Mycobacterium avium subsp. paratuberculosis MAP3464 gene encodes an oxidoreductase involved in invasion of bovine epithelial cells through the activation of host cell Cdc42.. Infection and immunity. 76(1):170-8.
Harriff MJ, Wu M, Kent ML, Bermudez LE. 2008. Species of environmental mycobacteria differ in their abilities to grow in human, mouse, and carp macrophages and with regard to the presence of mycobacterial virulence genes, as observed by DNA microarray hybridization.. Applied and environmental microbiology. 74(1):275-85.
Harriff MJ, Bermudez LE, Kent ML. 2007. Experimental exposure of zebrafish, Danio rerio (Hamilton), to Mycobacterium marinum and Mycobacterium peregrinum reveals the gastrointestinal tract as the primary route of infection: a potential model for environmental mycobacterial infection.. Journal of fish diseases. 30(10):587-600.
Bermudez LE, Motamedi N, Chee C, Baimukanova G, Kolonoski P, Inderlied C, Aralar P, Wang G, Phan LT, Young LS. 2007. EDP-420, a bicyclolide (bridged bicyclic macrolide), is active against Mycobacterium avium.. Antimicrobial agents and chemotherapy. 51(5):1666-70.
Danelishvili L, Wu M, Stang BV, Harriff M, Cirillo SLG, Cirillo S, Cirillo JD, Cirillo J, Bildfell RJ, Arbogast B et al.. 2007. Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection.. Proceedings of the National Academy of Sciences of the United States of America. 104(26):11038-43.