Analysis of the Leptospira proteins with putative hemolytic role thorough recombinant expression: detection of native expression, biological activity and vaccine potential

Author(s)

Enéas de Carvalho

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2008-05-16

Examining board members

Paulo Lee Ho; Thales de Brito; Aline Maria da Silva; Luis Eduardo Soares Netto; Paulo Hideki Yasuda

• Advisor: Paulo Lee Ho

Abstract

Leptospirosis is considered the most disseminated zoonosis of the world, and also a reemerging disease. This disease, caused by pathogenic bacteria of the genus Leptospira, has high rates of infection in developing countries, leading to severe economic and medical costs. There is not a licensed vaccine against leptospirosis for human use. After the genome sequencing of three species of leptospires, several genes were pointed to be promising vaccinal candidates. An important category of these candidates are those with putative hemolytic activity. In this work, we cloned and expressed some proteins with putative hemolytic activity. The recombinant proteins obtained, however, did not show hemolytic activity. One of these proteins, TlyC, was investigated with regard to its possible ability to interact to extracellular matrix (ECM) components. The results obtained indicate that TlyC binds with high affinity to several ECM components and that this protein can inhibit the Leptospira bind to a biological material that ressambles the ECM. The transcription and expression of these proteins were detected in leptospires cultures. Some of the recombinant proteins were used in an animal challenge against leptospirosis, but none of them were protective. We conclude that these proteins do not seem to be good vaccine candidates and that TlyC is a protein that interacts with the ECM and its components. (AU)