The OmpA-Like Protein Loa22 Is Essential for Leptospiral Virulence

Pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetic manipulations of pathogenic species. In this study, we characterized a mutant obtained by insertion of the transposon Himar1 into a gene encoding a putative lipoprotein, Loa22, which has a predicted OmpA domain based on sequence identity. The resulting mutant did not express Loa22 and was attenuated in virulence in the guinea pig and hamster models of leptospirosis, whereas the genetically complemented strain was restored in Loa22 expression and virulence. Our results show that Loa22 was expressed during host infection and exposed on the cell surface. Loa22 is therefore necessary for virulence of L. interrogans in the animal model and represents, to our knowledge, the first genetically defined virulence factor in Leptospira species

Experimental infection in tumor necrosis factor alpha receptor, interferon gamma and interleukin 4 deficient mice by pathogenic Leptospira interrogans

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-04-22T16:49:09Z No. of bitstreams: 1 Athanazio DA Experimental infection....pdf: 528649 bytes, checksum: 985c2ac201a23a656b1498a079f2ee62 (MD5)Made available in DSpace on 2014-04-22T16:49:09Z (GMT). No. of bitstreams: 1 Athanazio DA Experimental infection....pdf: 528649 bytes, checksum: 985c2ac201a23a656b1498a079f2ee62 (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, BrasilOnly recently, knockout mouse models were applied in studies on the pathogenesis of leptospirosis. Current data suggest an important role of innate immunity receptors and interferon gamma dependant cellular response on protection. It is not clear, however, whether T helper cell polarization influences on outcome of leptospiral infection. We report findings of experimental infection of C57BL/6 (interferon gamma or tumor necrosis factor alpha receptor deficient) and BALB/c (interleukin 4 deficient) mice infected by pathogenic Leptospira interrogans serovar Copenhageni. Specific cytokine gene deficiency had no impact on outcome since all animals survived. TNFR knockout mice, however, exhibited more severe residual renal inflammation during convalescence thus suggesting this cytokine is important in early control of infection, protecting kidneys from relevant pathology

An Imprint method for detecting leptospires in the hamster model of vaccine-mediated immunity for leptospirosis

Submitted by Martha Silveira Berbert ([email protected]) on 2011-04-25T19:02:54Z No. of bitstreams: 1 An imprint method for detecting leptospires.pdf: 220400 bytes, checksum: a7d90c3e814de07b78e40307f7d81071 (MD5)Made available in DSpace on 2011-04-25T19:02:54Z (GMT). No. of bitstreams: 1 An imprint method for detecting leptospires.pdf: 220400 bytes, checksum: a7d90c3e814de07b78e40307f7d81071 (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Bio-Manguinhos, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilIn determining the efficacy of new vaccine candidates for leptospirosis, the primary end point is death and an important secondary end point is sterilizing immunity. However, evaluation of this end point is often hampered by the time-consuming demands and complexity of methods such as culture isolation (CI). In this study, we evaluated the use of an imprint (or touch preparation) method (IM) in detecting the presence of leptospires in tissues of hamsters infected with Leptospira interrogans serovar Copenhageni. In a dissemination study, compared to CI, the IM led to equal or improved detection of leptospires in kidney, liver, lung and blood samples collected post-infection and overall concordance was good (kappa=0.61). Furthermore, in an evaluation of hamsters immunized with a recombinant leptospiral protein-based vaccine candidate and subsequently challenged, the agreement between the CI and IM was very good (kappa=0.84). These findings indicate that the IM is a rapid method for the direct observation of Leptospira spp. that can be readily applied to evaluating infection in experimental animals and determining sterilizing immunity when screening potential vaccine candidates