RESUMO

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.

Assuntos

RESUMO

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.

RESUMO

Leptospirosis is a zoonosis caused by the pathogenic bacteria of the genus Leptospira. The identification of conserved outer membrane proteins among pathogenic strains is a major research target in elucidating mechanisms of pathogenicity. Surface-exposed proteins are most probably the ones involved in the interaction of leptospires with the environment. Some spirochetes use outer membrane proteases as a way to penetrate host tissues. HtrA is a family of proteins found in various cell types, from prokaryotes to primates. They are a set of proteases usually composed of a serine protease and PDZ domains, and they are generally transported to the periplasm. Here, we identified four genes-annotated as HtrA, LIC11111, LIC20143, LIC20144 and LIC11037-and another one annotated as a serine protease, LIC11112. It is believed that the last forms a functional heterodimer with LIC11111, since they are organized in one operon. Our analyses showed that these proteins are highly conserved among pathogenic strains. LIC11112, LIC20143, and LIC11037 have the serine protease domain with the conserved catalytic triad His-Asp-Ser. This is the first bioinformatics analysis of HtrA proteins from Leptospira that suggests their proteolytic activity potential. Experimental studies are warranted to elucidate this possibility.

RESUMO

Leptospirosis is a zoonosis caused by the pathogenic bacteria of the genus Leptospira. The identification of conserved outer membrane proteins among pathogenic strains is a major research target in elucidating mechanisms of pathogenicity. Surface-exposed proteins are most probably the ones involved in the interaction of leptospires with the environment. Some spirochetes use outer membrane proteases as a way to penetrate host tissues. HtrA is a family of proteins found in various cell types, from prokaryotes to primates. They are a set of proteases usually composed of a serine protease and PDZ domains, and they are generally transported to the periplasm. Here, we identified four genes—annotated as HtrA, LIC11111, LIC20143, LIC20144 and LIC11037—and another one annotated as a serine protease, LIC11112. It is believed that the last forms a functional heterodimer with LIC11111, since they are organized in one operon. Our analyses showed that these proteins are highly conserved among pathogenic strains. LIC11112, LIC20143, and LIC11037 have the serine protease domain with the conserved catalytic triad His-Asp-Ser. This is the first bioinformatics analysis of HtrA proteins from Leptospira that suggests their proteolytic activity potential. Experimental studies are warranted to elucidate this possibility.

RESUMO

Leptospirosis is a neglected infectious disease of global importance. Vaccination is the most viable strategy for the control of leptospirosis, but in spite of efforts for the development of an effective vaccine against the disease, few advances have been made, and to date, bacterin is the only option for prevention of leptospirosis. Bacterins are formulations based on inactivated leptospires that present a series of drawbacks, such as serovar-dependence and short-term immunity. Therefore, bacterins are not widely used in humans, and only Cuba, France and China have these vaccines licensed for at-risk populations. The development of recombinant DNA technology emerges as an alternative to solve the problem. Recombinant protein-based vaccines or DNA vaccines seem to be an attractive strategy, but the use of adjuvants is critical for achievement of a protective immune response. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells. In the last years, several components have been tested as adjuvants, such as aluminum salts, oil based-emulsion adjuvants, bacteria-derived components and liposomes. This review highlights the use of adjuvants in the multiple vaccine approaches that have been used for leptospirosis and their most important immunological aspects. Immune response data generated by these strategies can contribute to the understanding of the immune mechanisms involved in protection against leptospirosis, and consequently, the development of effective vaccines against this disease. This is the first review on leptospiral vaccines focusing on adjuvant aspects.

Assuntos

RESUMO

Leptospirosis is a neglected infectious disease of global importance. Vaccination is the most viable strategy for the control of leptospirosis, but in spite of efforts for the development of an effective vaccine against the disease, few advances have been made, and to date, bacterin is the only option for prevention of leptospirosis. Bacterins are formulations based on inactivated leptospires that present a series of drawbacks, such as serovar-dependence and short-term immunity. Therefore, bacterins are not widely used in humans, and only Cuba, France and China have these vaccines licensed for at-risk populations. The development of recombinant DNA technology emerges as an alternative to solve the problem. Recombinant protein-based vaccines or DNA vaccines seem to be an attractive strategy, but the use of adjuvants is critical for achievement of a protective immune response. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells. In the last years, several components have been tested as adjuvants, such as aluminum salts, oil based-emulsion adjuvants, bacteria-derived components and liposomes. This review highlights the use of adjuvants in the multiple vaccine approaches that have been used for leptospirosis and their most important immunological aspects. Immune response data generated by these strategies can contribute to the understanding of the immune mechanisms involved in protection against leptospirosis, and consequently, the development of effective vaccines against this disease. This is the first review on leptospiral vaccines focusing on adjuvant aspects.

Assuntos