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Heterologous expression of the gene LIC13259 in the saprophyte Leptospira biflexa and their acquisition capacity to evade the human immune system

Grant number: 18/08131-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2019
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Ana Lucia Tabet Oller Do Nascimento
Grantee:Maria Fernanda Cavenague Pereira
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis, AP.TEM

Abstract

Leptospirosis is a global zoonosis that affects several animal species, including humans, caused by pathogenic species of the genus Leptospira. It has a very varied clinical manifestation. It can present, from common symptoms, tropical diseases, such as fever, chills, headaches, muscle aches, nausea, vomiting and diarrhea, to a severe syndrome of multisystemic infection known as Weil's Syndrome. Several factors of virulence and proteins involved in the invasion and evasion of the host have been identified. Our group has been studying new surface genes of this bacterium and very interesting results have been obtained, for example, those of the protein encoded by the LIC13259 gene studied during the master's degree showed to be able to contribute to the colonization, invasion and immune evasion process of the host. However, the conditions employed in these studies were with the recombinant proteins and purified components and a more complex biological system is necessary in order to validate the activities found. Thus, the present project proposes to obtain knock-in mutants of the L. biflexa saprophytic strain, which does not have the LIC13259 gene and to evaluate if the saprophytic leptospires acquire adhesion activity, evaluating the binding of the mutated strain with components of the extracellular matrix, the acquisition of serum plasminogen and generation of plasmin, and finally the ability to survive normal human serum, considering that saprophytic strains are sensitive and pathogenic resistant. Still in the line of research to look for virulence factors, the project proposes to characterize a new coding sequence, LIC12254, that contains RGD domain with capacity to interact with human integrins and to play important functions in the invasion of the pathogen. In this way, the project will contribute to a better understanding of the pathogenicity of L. Interrogans. (AU)