EVALUATION OF TYPE I AND TYPE III FRIMBRIAE COMPONENTS AS VACCINE CANDIDATES AGAINST Klebsiella pneumoniae INFECTIONS

• Grant number: 23/10579-8
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2023 - November 30, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Michelle Darrieux Sampaio Bertoncini
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated researchers: Thiago Rojas Converso
• Associated scholarship(s): 24/06054-0 - Recombinant production and functional evaluation of type I and III fimbriae from Klebsiella pneumoniae, BP.TT

Abstract

Klebsiella pneumoniae is a Gram-negative bacterium that commonly colonizes human mucosae, from where it can spread and cause serious infections, affecting mainly children, the elderly and immunocompromised patients. The high morbidity and mortality rates associated with K. pneumoniae, coupled with the alarming increase in antimicrobial resistance, encourage the development of strategies to prevent these infections. In that sense, vaccines based on surface proteins are a promising approach since these antigens are usually conserved among clinical strains and accessible to the host immune system. Fimbriae are macromolecular structures exposed at the bacterial surface that play a role in adhesion and biofilm formation. K. pneumoniae expresses two types of fimbriae, I and III, that are important for its virulence. The present work aims to investigate the vaccine potential of K. pneumoniae fimbriae subunits in mouse infection models. The antigens will be produced as recombinant proteins in E. coli, purified and used to immunize mice. The immune responses will be characterized, and protection will be assessed against urinary and respiratory infections, as well as sepsis. The induced antibodies will be evaluated in functional assays to test their ability to bind to the native fimbriae on the bacterial surface, promote complement deposition and phagocytic killing. The effect of antibodies on biofilms formation and bacterial adhesion to respiratory and urinary epithelial cells will also be investigated. In parallel, we propose a new model of biofilm formation in epithelial cells culture, mimicking the initial steps of common infections caused by this pathogen. This model will be used to evaluate the contribution of frimbriae to biofilm formation, by comparing wild type strains and mutants that do not express fimbriae components. Take together, the results of this study should contribute to the development of prophylactic measures against K. pneumoniae and help understand the role of fimbriae in bacterial virulence. (AU)