The Leptospira interrogans LIC10774 is a multifunctional surface protein that binds calcium and interacts with host components

Microbiol Res. 2020 May:235:126470. doi: 10.1016/j.micres.2020.126470. Epub 2020 Mar 19.

Abstract

Leptospirosis is a global re-emerging zoonosis, caused by pathogenic bacteria of the genus Leptospira. Humans are infected mainly through contact with contaminated water or soil. The understanding of the molecular mechanisms of leptospirosis through the characterization of unknown outer membrane proteins may contribute to the development of new treatments, diagnostic methods and vaccines. We have identified using bioinformatics analysis a protein that is encoded by the gene LIC10774, predicted to be localized at the leptospiral outer membrane and exhibit beta-roll folding. Surface exposure was confirmed by flow cytometry, ELISA and immunofluorescence-based confocal microscopy. Through circular dichroism spectroscopy and hydrophobic dye binding we have shown that rLIC10774 binds calcium ions, which imposes changes to secondary and tertiary structures. The recombinant protein was capable of binding to several host extracellular matrix and serum components. Therefore, we describe LIC10774 as a calcium-binding protein exposed in the outer surface of pathogenic leptospires with possible multifunctional roles in adhesion to host tissues, evasion of the immune system and participation in dissemination processes during leptospirosis. In addition, we hypothesize that the calcium binding is important for temperature-dependent functional roles during leptospirosis.

Keywords: Calcium-binding protein; Host-pathogen-interactions; Leptospira; Leptospirosis; Outer-membrane-proteins.

MeSH terms

  • Animals
  • Bacterial Adhesion
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Calcium / metabolism*
  • Cloning, Molecular
  • Computational Biology
  • Female
  • Host-Pathogen Interactions*
  • Humans
  • Leptospira interrogans / genetics*
  • Leptospira interrogans / pathogenicity
  • Mice
  • Mice, Inbred BALB C
  • Protein Binding
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology

Substances

  • Bacterial Outer Membrane Proteins
  • Recombinant Proteins
  • Calcium