David A. Haake, M.D.
Leptospirosis. The focus of our research is to elucidate the molecular mechanisms of pathogenesis and immunity mediated by outer membrane proteins (OMPs). Our laboratory has developed strategies for membrane fractionation and identification of surface-exposed OMPs. We identified a family of leptospiral immunoglobulin-like repeat (Lig) proteins that are targeted by the human immune response to leptospirosis. When virulent leptospires are exposed to host-physiologic levels of osmolarity, expression of LigA and LigB is dramatically increased. We found that the LigA and LigB bind host extracellular matrix proteins, indicating roles for Lig proteins in host tissue colonization. Recent studies indicate that the Lig proteins are extremely promising immunodiagnostic and vaccine antigens. Research supported by the National Institutes of Health (NIAID award R01 AI034431) and VA Medical Research Funds.
Rapid bacterial pathogen identification and antibiotic susceptibility testing. Our electrochemical sensor assay was developed by a multidisciplinary team of scientists and involves “sandwich” hybridization of target 16S rRNA to species-specific capture and detector probes. Horseradish peroxidase coupled to the detector probe provides a redox signal that is reported as electrical current. The assay can be performed at room temperature, has the sensitivity to defect as few as 100 bacteria, and can be performed in less than 30 minutes. The sensor assay can identify and quantitate pathogens in clinical specimens, and also assess the susceptibility of pathogens to antibiotics. Rapid detection of drug-resistant bacterial pathogens would revolutionize the diagnosis and treatment of infectious diseases. Research supported by the National Institutes of Health (NIAID award U01 AI075565).
Kothari, A., Morgan, M., Haake, D. A. “Emerging technologies for rapid identification of bloodstream pathogens,”Clin. Infect. Dis. 59:272-8 (2014).
Lourdault, K., Wang, L.-C., Vieira, A., Melo, R., Gomes-Solecki, M., Haake, D. A. “Oral immunization with LigA induces a protective immune response to Leptospira interrogans serovar Copenhageni strain L1-130,” Infect. Immun. 82:893-902 (2014).
Evangelista, K. V., Hahn, B., Wunder, E. A. Jr., Ko, A. I., Haake, D. A., and Coburn, J. “Identification of cell-binding adhesins of Leptospira interrogans,” PLoS Negl. Trop. Dis. 8:e3215 (2014).
Witchell, T. D., Eshghi, A., Nally, J. E., Hof, R., Boulanger, M. J., Wunder, E. A. Jr., Ko, A. I., Haake, D. A., and Cameron, C. E., “Post-translational modification of LipL32 during Leptospira interrogans infection,” PLoS Negl. Trop. Dis. 8(10):e3280 (2014).
Coutinho, M. L., Matsunaga, J., Lewis, M., Babbitt, J. T., Aleixo, J. A. G., and Haake, D. A. “The kinetics of infection and host response reveals insights into pathogenesis of leptospirosis” PLoS Negl. Trop. Dis. 8(11):e3307 (2014).
Levett, P. N. and Haake, D. A., “Leptospira Species (Leptospirosis).” In: Mandell, G. L., Bennett, J. E., and Dolin, R., eds. Principles and Practices of Infectious Diseases, Eighth Edition, Elsevier, Amsterdam, Chapter 240 (2014).
Haake, D. A. and Zückert, W. R., “The Leptospiral Outer Membrane,” Curr. Top. Microbiol. Immunol. 387:187-221 (2015). PMID: 25388136
Haake, D. A. and Levett, P. N., “Human Leptospirosis.” Curr Top Microbiol Immunol. 387: 65-97 (2015).
Scott, V. C. S., Haake, D. A., Churchill, B. M., Justice, S. S., and Kim, J.-H., “Intracellular bacterial communities: A potential etiology for chronic lower urinary tract symptoms,” Urology 86:425-31 (2015).
Narayanavari, S. A., Lourdault, K., Sritharan, M., Haake, D. A., and Matsunaga, J. “Role of sph2 gene regulation in hemolytic and sphingomyelinase activities produced by Leptospira interrogans” PLoS Negl. Trop. Dis. 9(8):e0003952 (2015).
Wunder, E. A., Figueira, C. P., Santos, G. R., Lourdault, K., Matthias, M. A., Vinetz, J. M., Ramos, E., Haake, D. A., Picardeau, M., Dos Reis, M. G., Ko, A. I. “Real-time PCR reveals rapid dissemination of Leptopspira interrogans after intraperitoneal and conjunctival inoculation of hamsters” Infect. Immun. 84:2105-2115 (2016).
Lourdault, K., Matsunaga, J., Haake, D. A. “High-thoughput parallel sequencing to measure fitness of Leptospira interrogans transposon insertion mutants during acute infection” PLoS Negl. Trop. Dis. 10(11):e0005117 (2016).