Research Summary

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 R21 AI128560) and VA Medical Research Funds.

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Selected Publications

Patel, R., Polage, C. R., Bard, J.D., May, L., Lee, F.M., Fabre, V., Hayden, M.K., Doernberg, S.D.B., Haake, D.A., Trautner, B.W., Grigoryan, L., Tsalik, E.L., and Hanson, K.E. “Envisioning future urinary tract infection diagnostics,” Clin Infect Dis. 74(7):1284-1292. April 9, 2022. PMID: 34463708.

Haake, D. A. and Matsunaga, J. “Leptospiral immunoglobulin-like domain proteins: Roles in virulence and immunity,” Front. Immunol. January, 2021. PMID: 33488581.

Wu, S., Huang, G., de St. Maurice, A., Lehman, D., Graber, C., Goetz, M. B., and Haake, D. A. “The impact of rapid species identification on management of bloodstream infections. What’s in a name?” Mayo Clin. Proceed. November, 2020.

Markowitz, M. A., Monti, G. K., Kim, J.-H., and Haake, D. A. “Rapid diagnostic testing in the management of urinary tract infection: Potentials and limitations,” Diag Microbiol Infect Dis., Mar 5 (2019). PMID:30928179

Matsunaga, J., Haake, D. A. “cis-acting determinant limiting expression of sphingomyelinase gene sph2 in Leptospira interrogans, identified with a gfp reporter plasmid,” App Env Microbiol 84:e02068-18 (2018).

Haake, D. A. and Zückert, W. R., “Spirochetal Lipoproteins in Pathogenesis & Immunity,” Curr. Top. Microbiol. Immunol. December 2, 2017. PMID 29196824

Ratet, G., Santecchia, I., Fanton d’Andon, M., Vernel-Pauillac, F., Wheeler, R., Lenormand, P. Fischer, F., Haake, D. A., Picardeau, M., Bonec, I. G., Werts, C. “LipL21 lipoprotein binding to peptidoglycan enables Leptospira interrogans toescape from NOD recognition” PLoS Pathogens 13:e1006725 (2017).

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).

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).

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).

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).

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).

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).