The HtrA Protease of Borrelia Burgdorferi Degrades Outer Membrane Protein BmpD and Chemotaxis Phosphatase CheX

Mol Microbiol. 2013 May;88(3):619-33. doi: 10.1111/mmi.12213. Epub 2013 Apr 9.

Abstract

Borrelia burgdorferi, the spirochaetal agent of Lyme disease, codes for a single HtrA protein, HtrABb (BB0104) that is homologous to DegP of Escherichia coli (41% amino acid identity). HtrABb shows physical and biochemical similarities to DegP in that it has the trimer as its fundamental unit and can degrade casein via its catalytic serine. Recombinant HtrABb exhibits proteolytic activity in vitro, while a mutant (HtrABbS198A) does not. However, HtrABb and DegP have some important differences as well. Native HtrABb occurs in both membrane-bound and soluble forms. Despite its homology to DegP, HtrABb could not complement an E. coli DegP deletion mutant. Late stage Lyme disease patients, as well as infected mice and rabbits developed a robust antibody response to HtrABb, indicating that it is a B-cell antigen. In co-immunoprecipitation studies, a number of potential binding partners for HtrABb were identified, as well as two specific proteolytic substrates, basic membrane protein D (BmpD/BB0385) and chemotaxis signal transduction phosphatase CheX (BB0671). HtrABb may function in regulating outer membrane lipoproteins and in modulating the chemotactic response of B. burgdorferi.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Borrelia burgdorferi / genetics*
  • Borrelia burgdorferi / growth & development
  • Chemotaxis / genetics
  • Escherichia coli / genetics
  • Gene Deletion
  • Genetic Complementation Test
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Immunoprecipitation
  • Lyme Disease / microbiology
  • Mice
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction

Substances

  • Bacterial Proteins
  • BmpD protein, Borrelia burgdorferi
  • Heat-Shock Proteins
  • Periplasmic Proteins
  • Recombinant Proteins
  • Phosphoric Monoester Hydrolases
  • DegP protease
  • Serine Endopeptidases