Evaluation of bactericidal and opsonizing effects of lactoferrin on Streptococcus pneumoniae

• Grant number: 11/22633-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2012
• End date: May 31, 2014
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Michelle Darrieux Sampaio Bertoncini
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Lactoferrina is an important component of the innate immune system, which protects mucosal surfaces against many pathogenic microrganisms, due to its bactericidal, bacteriostatic and immunomodulating effects. S. pneumoniae is partially resistant against lactoferrin's lytic effects, due to the presence of the protein PspA on its surface, which inhibits lactoferrin's proteolisis, na essencial step in the bactericidal mechanism of this protein. It hás been demonstrated, however, that anti-PspA antibodies are able to amplify LF's lytic effect on S. pneumoniae in vitro. Also, the adition of recombinant PspA abrogates LF's function, posssibly through competitive binding and stabilization of LF. Since PspA is a serologically variable protein, the present work aims at investigating the width of lactoferrin's effect over S. pneumonia bering distinct PspAs. Initially, the cross-protective role of anti-PspA antibodies in mediating lactoferrin-induced lysis will be investigated. Also, the potential of diverse recombinant PspA fragments to abrogate LF's activities will be evaluated. LF's potential to increase phagocytosis of wild type and PspA-negative S. pneumoniae will be investigated using mouse and human leucocytes. Finally, the in vivo effects of lactoferrin will be analysed through incubation of bactéria with Lf, folowed by experimental lung infection in mice, also comparing wild type and PspA negative strains.Altogether, the results of the present project will contribute to the elucidation of the mechanisms involved in pneumococcal clearance during the initial steps of infection. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDRE, G. O.; POLITANO, W. R.; MIRZA, S.; CONVERSO, T. R.; FERRAZ, L. F. C.; LEITE, L. C. C.; DARRIEUX, M.. Combined effects of lactoferrin and lysozyme on Streptococcus pneumoniae killing. Microbial Pathogenesis, v. 89, p. 7-17, DEC 2015. (11/22633-0)