Research

Function

Our laboratory developed strategies for membrane fractionation and identification of proteins exposed on the surface of Leptospira interrogans and identified a number of transmembrane and lipoprotein OMPs. We identified a family of leptospiral immunoglobulin-like repeat (Lig) proteins that are targeted by the human immune response in leptospirosis. We found that LigA and LigB bind tightly to host ligands and inhibit fibrin formation. In collaboration with Mathieu Picardeau and Albert Ko, we developed a surrogate host expression system for assessing the contribution of leptospiral OMPs to the adhesion phenotype of leptospiral cells.

Gene Regulation

We have shown that virulent leptospires dramatically increase expression of LigA and LigB in response to temperature and host-physiologic levels of osmolarity. We have identified the region upstream of the promoter that determines expression levels of the leptospiral sphingomyelinase gene, sph2. In collaboration with Ben Adler and Richard Zuerner, we have examined the whole-genome transcriptional response to osmolarity, temperature, and low-iron conditions found in host tissues.

Vaccine

Using a combination of the porin, OmpL1, and the surface lipoprotein, LipL41, we were the first to demonstrate protection with recombinant proteins in an animal model of leptospirosis. Recent vaccine studies have focused on the Lig proteins. We have shown that LigA is a potent protective immunogen, and we have localized the key LigA protective epitopes to domains 10 through 13. We have also shown that LigA can mediate protection as an oral vaccine, with potential usefulness in reservoir host animals.

Links & Resources

More information about leptospirosis:

Links of interest to leptospirosis researchers:

Upcoming meetings of interest to leptospirosis researchers:

  • The 2024 International Leptospirosis Conference will be held in Brussels, Belgium in September, 2024.
  • The next Gordon Research Conference on the Biology of Spirochetes will be held in 2024.

References

1. Haake DA, Matsunaga J. Leptospira: a spirochaete with a hybrid outer membrane. Mol Microbiol. 2010;77:805-14.

2. Pinne M & Haake, DA.  A comprehensive approach to identification of surface-exposed outer membrane-spanning proteins of Leptospira interrogans.  PLoS ONE. 2009; 4:e6071.

3. Matsunaga J, Barocchi MA, Croda J, Young TA, Sanchez Y, Siqueira I, et al. Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Mol Microbiol. 2003;49(4):929-45.

4. Choy HA, Kelley MM, Croda J, Matsunaga J, Babbitt JT, Ko AI, et al. The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans. PLoS ONE. 2011;6:e16879.

5. Figueira CP, Croda J, Choy HA, Haake DA, Reis MG, Ko AI, Picardeau M. Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexa confers enhanced adhesion to cultured cells and extracellular matrix components. BMC Microbiology. 2011;11:129.

6. Galperin MY. A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts. BMC Microbiol. 2005;5:35.

7. Matsunaga J, Lo M, Bulach DM, Zuerner RL, Adler B, Haake DA. Response of Leptospira interrogans to physiologic osmolarity: relevance in signaling the environment-to-host transition. Infect Immun. 2007;75(6):2864-74.

8. Silva EF, Medeiros MA, McBride AJ, Matsunaga J, Esteves GS, Ramos JB, et al. The terminal portion of leptospiral immunoglobulin-like protein LigA confers protective immunity against lethal infection in the hamster model of leptospirosis. Vaccine. 2007;25:6277-86.

9. Coutinho ML, Choy HA, Kelley MM, Matsunaga J, Babbitt JT, Lewis M, et al. A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans. PLoS Negl Trop Dis. 2011 December; 5(12); e1422.