UTMB Department of Pathology

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Pathogenesis of Obligate Intracellular Bacteria

My research interests are focused on the pathogenesis of obligate intracellular bacteria, namely rickettsiae and ehrlichiae.

I have two funded projects in rickettsial diseases. The first project focuses on the development of ultrasensitive diagnostic methods (electrochemilumiscence and tyramide-based amplification) for rickettsial infections during the acute phase of the disease. The second project focuses on molecular pathogenesis of rickettsioses and development of novel anti-rickettsial treatment by combinatorial peptide-based libraries. The project uses combinatorial peptide-based libraries coded within pantropic retroviruses. Retroviruses are used to infect cell monolayers that will be challenged with rickettsial pathogens. Cells that survive the challenge will be selected and possible molecular mechanisms responsible for their resistant phenotype will be elucidated. This project is funded by the US army and it is done in collaboration with the Department of Human Biological Chemistry and Genetics and the Department of Microbiology. Another aim of this project is to elucidate the molecular mechanisms underlying the increased vascular permeability seen in rickettsioses. Such increased vascular permeability leads to cerebral and pulmonary edema, the two main causes of morbidity and mortality in human rickettsioses.

Techniques used in this project include in vitro measurements of intracellular calcium by fluorescent microscopy, signal transduction pathways affecting cytoskeletal proteins, measurements of vascular permeability in vivo and in vitro using Electronic Cell-Substrate Impedance Sensing (ECIS) and FITC labeled dextrans.

My work on ehrlichial pathogens focuses on the epidemiology and the study of the immune mechanisms responsible for the control of these infections. My involvement in this project includes the development of animal models for the study of ehrlichiosis.

1. Feng HM, Whitworth T, Olano JP, Popov VL, Walker DH. Fc-dependent polyclonal antibodies and antibodies to outer membrane proteins A and B, but not lipopolysaccharide, protect SCID mice against fatal Rickettsia conorii infection. Inf Immun.72:2222-2228;2004
2. Olano JP, Wen G, Feng HM, McBride JW, Walker DH. Histologic, serologic, and molecular analysis of persistent ehrlichiosis in a murine model. Am J Path. 165:997-1006;2004
3. Ismail N, Soong L, Olano JP, Walker DH. Overproduction of TNF- and downregulation of IFN--dominated Th1 response contribute to toxic shock-like syndrome in an animal model of fatal human monocytotropic ehrlichiosis. J Immunol.172:1786-1800;2004
4. Sha J, Kozlova EV, Fadl AA, Olano JP, Chopra AK. Molecular characterization of a glucose inhibition division gene (gidA) that regulates virulence of Aeromonas hydrophila. Inf Immun.72:1084-1095;2004
5. Galvao M, Dumler JS, Mafra CL, Calic SB, Chamone CB, Cesarino Filho G, Olano JP, Walker DH: Fatal spotted fever rickettsiosis in the state of Minas Gerais: a re-emerging infectious disease in Brazil. Emerg Infect Dis. 9:1402-1406;2003
6. Olano JP, Hogrefe W, Seaton B and Walker DH. Clinical manifestations epidemiology and laboratory diagnosis of human monocytotropic ehrlichiosis in a commercial laboratory setting. Clin Diag Lab Immun. 10:891-896;2003
7. Zhen L, Diaz-Montero M, Yu XJ, Olano JP, Feng HM, Walker DH. Identification of CD8 T-lymphocyte epitopes in OmpB of Rickettsia conorii. Infect Immun.71:3920-3926;2003
8. Gessell-Lee D, Popov VL, Boldogh I, Olano JP, Peterson JW. The role of cyclooxygenase enzymes in a murine model of experimental cholera. Infect Immun.71(11):6234-6242;2003
9. Olano JP, Masters E, Hogrefe W, Walker DH. Human Monocytotropic Ehrlichiosis, Missouri. Emerging Infect Dis.9:1579-1586;2003
10. Billings AN, Feng HM, Olano JP and Walker DH. Rickettsial infection in murine models activates an early anti-rickettsial effect mediated by NK cells and associated with production of gamma interferon. Am J Trop Med Hyg.65:52-56;2001
11. Sotomayor E, Popov VL, Feng HM, Walker DH and Olano JP. Animal model of human monocytotropic ehrlichiosis. Am J Path.158(2):757-769;2001
12. Walker DH, Olano JP and Feng HM. The critical role of cytotoxic T-lymphocytes in immune clearance of rickettsial infection. Infect Immun.69:1841-1846;2001
13. Olano JP., Holmes H., Woods GL. Evaluation of the Myko AKT latex agglutination test for rapid diagnosis of Mycobacterium avium complex infections. Diagnostic Microbiology and Infectious Disease.30:71-74; 1998.
14. Sexton DJ, Corey RG, Carpenter C, Kong LQ, Gandhi T, Breitschwerdt E, Hegarty B, Chen SM, Feng HM, Yu XJ, Olano JP, Walker DH, Dumler SJ. Dual infection with Ehrlichia chaffeensis and a spotted fever group rickettsia. Emerging Infectious Diseases.4:311-17;1998
15. Gelman BB., Wolf DA., Olano JP., Linthicum L. Environmental influences on the pathology of the acquired immunodeficiency syndrome. Autopsy results in Texas prison inmates. Human Pathology. 27(12):1282- 7; 1996.
16. Olano JP., Wolf W., Keherly M., and Gelman BB. Quantifying apoptosis in banked human brains using flow cytometry. J of Neuropathology and Experimental Neurology.55(11):1164-72; 1996
17. Olano JP., Borucki M., Wen J., Haque A. Massive hepatic steatosis and lactic acidosis in HIV-seropositive patient receiving prophilactic AZT. Clinical Infectious Diseases. 21:973-6; 1995

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