 |
|
|
Kathleen D. Eisenach
Professor, Department of Pathology and Department of Microbiology & Immunology Bacteriology Research Interest: Tuberculosis diagnostics, molecular epidemiology of tuberculosis, surrogate markers of response to antituberculosis drugs, and differential pathogenesis of clinical strains of Mycobacterium tuberculosis. Ph.D ., Microbiology and Immunology, University of Arkansas for Medical Sciences Phone: (501) 257-4826 Research Description Our laboratory has a long history of being involved in research with Mycobacterium tuberculosis and other commonly encountered mycobacteria. M. tuberculosis is the bacterial agent that causes tuberculosis in humans, M. bovis causes bovine tuberculosis, M. bovis BCG is used as vaccine in some parts of the world, and M. avium causes disseminated infections in AIDS patients. Investigators in our laboratory were the first to describe plasmids in mycobacteria, resistance to phage infection in mycobacteria mediated by plasmids, presence of plasmids in most M. avium isolated from blood cultures of patients having AIDS, and an insertion sequence (IS6110) which is unique to M. tuberculosis and M. bovis . Tuberculosis is a major health problem in the world. The incidence is increasing in the U.S., mainly affecting the elderly, minority groups, HIV-infected persons, and foreign born. Control of this tuberculosis epidemic depends on the availability of rapid diagnosis and treatment. In recent years our work has focused on developing a diagnostic assay based on the polymerase chain reaction (PCR) and a molecular technique (DNA fingerprinting) for typing M. tuberculosis strains. The PCR assay amplifies the insertion sequence IS6110 directly in clinical specimens on the same day they are collected. Currently we are evaluating the assay for its usefulness in diagnosing tuberculosis and monitoring the response of patients receiving antituberculosis therapy. A collaboration with industry involves developing another diagnostic assay based on strand displacement amplification technology. The DNA fingerprinting technique depends on the unique distribution of IS6110 within the chromosome of each strain. It is being used for tracing the spread of strains in outbreaks of tuberculosis, determining the mechanism of transmission in high-risk populations (prisons, homeless shelters, etc.) and in a defined geographic area (Arkansas), and investigating outbreaks of bovine tuberculosis in cattle and game farm animals. A common goal of those involved in mycobacterial research is to understand the virulence of M. tuberculosis. Much effort is now focused on identifying at the molecular level the properties of M. tuberculosis which are responsible for causing disease. Obtaining detailed information on the structure of mycobacterial genomes and having the ability to transfer genes between mycobacterial strains will undoubtedly provide new insights. Toward this end, we continue our studies with IS6110 to demonstrate transposition and characterize the sites of insertion. We are isolating genes involved with iron regulation and creating mycobacterial vectors using the origin of replication from a M. avium plasmid. Another important goal is to understand mycobacterial persistence. The nature of tuberculosis as a reactivation disease and the requirement of extended chemotherapy suggests an ability of M. tuberculosis to persist in some "dormant" form in infected tissues. We are beginning a new project to identify genes that are specifically expressed in the latent stage of infection. Understanding the molecular basis of persistence will have a profound effect on disease control. References Theus, SA Cave, MD, Eisenach, KD. 2005. Intracellular macrophage growth rates and cytokine profiles of Mycobacterium tuberculosis strains with different transmission dynamics. J Infect Dis 191(3):453-60. Cronje L, Edmondson N, Eisenach KD, Bornman L. 2005. Iron and iron chelating agents modulate Mycobacterium tuberculosis growth and monocyte-macrophage viability and effector functions. FEMS Immunol Med Microbiol 45(2): 103-12. Cave MD, Yang AH, Stefanova R, Fomukong N, Ijaz K, Bates J, Eisenach KD. 2005. Epidemiologic import of tuberculosis cases whose isolates have similar but not identical IS6110 restriction fragment length polymorphism patterns. J Clin Microbiol 43:1228-1233. Hazbon MH, del Valle MB, Guerrero MI, Varm-Basil M, Filliol I, Eisenach KD, Sifuentes-Osornio J, de Leon AP, Cave MD, Alland D. 2005. Role of embB condon 306 mutations in Mycobacterium tuberculosis revisted: a novel association with broad drug resistance and IS6110 cluster rather than ethambutol resistance. Antimicrob Agents Chemo 49:3794-3802. Filliol I, Motiwala AS, Cavatore M, Qi W, Hazbón MH, Bobadilla del Valle M, Fyfe J, García-García L, Rastogi N, Sola C, Zozio T, Guerrero MI, León CI, Crabtree J, Angiuoli S, Eisenach KD, Durmaz R, Joloba ML, Rendón A, Sifuentes-Osornio J, Ponce de León A, Cave MD, Fleischmann R, Whittam TS, Alland D. 2006. The Global Phylogeny of Mycobacterium tuberculosis based on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set. J Bacteriol 188:759-772. Hazbón MH, Brimacombe M, Bobadilla del Valle M, Cavatore M, Guerrero MI, Varma-Basil M, Billman-Jacobe H, Lavender C, Fyfe J, García-García L, León CI, Bose M, Chaves F, Murray M, Eisenach KD, Sifuentes-Osornio J, Cave MD, Ponce de León A, Alland D. 2006. Population Genetics Study of Isoniazid Resistance Mutations and Evolution of Multidrug-Resistant Mycobacterium tuberculosis. Antimicrob Agents Chemo 50: 2640-2649. Johnson J, Hadad DJ, Boom H, Daley CL, Peloquin CA, Eisenach KD, Jankus DD, Debanne SM, Charleboise ED, Maciel E, Palaci M, Dietze R. 2006. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis10:605-12. Muhumuza J, Asiimwe BB, Kayes SS, Mugyenyi P, Whalen C, Mugerwa RD, Boom H, Eisenach KD, Joloba M. 2006. Introduction of an in-house PCR for routine identification of M. tuberculosis complex in low income country. Int J Tuberc Lung Dis 10:1262-1267. Theus SA, Cave MD, Eisenach KD, Walrath J, Lee H, Mackay W, Whalen C, Silver RF. 2006. Differences in the growth of paired Ugandan isolates of Mycobacterium tuberculosis within human mononuclear phagocytes correlate with epidemiological evidence of strain virulence. Infect Immun 74:6865-76. Traore H, Ogwang S, Mallard K, Joloba ML, Mumbowa F, Narayan K, Kayes S, Jones-Lopez EC, Smith PG, Ellner JJ, Mugerwa RD, Eisenach KD, McNerney R. 2007. Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda. Ann Clin Microbiol Antimicrob 6:1-6.
Questions about this page? Send us an email. |
 |
||||||||||||||||||||||||||||||||||||||
