Functional analysis of the Listeria monocytogenes secretion chaperone PrsA2 and its multiple contributions to bacterial virulence

Mol Microbiol. 2011 Jun;80(6):1530-48. doi: 10.1111/j.1365-2958.2011.07665.x. Epub 2011 May 5.

Abstract

As an organism that has evolved to live in environments ranging from soil to the cytosol of mammalian cells, Listeria monocytogenes must regulate the secretion and activity of protein products that promote survival within these habitats. The post-translocation chaperone PrsA2 has been adapted to assist in the folding and activity of L. monocytogenes secreted proteins required for bacterial replication within host cells. Here we present the first structure/function investigation of the contributions of PrsA2 to protein secretion and activity as well as to bacterial virulence. Domain swap experiments with the closely related L. monocytogenes PrsA1 protein combined with targeted mutagenesis indicate distinct functional roles for the PrsA2 peptidyl-prolyl isomerase (PPIase) and the N- and C-terminal domains in pathogenesis. In contrast to other PrsA-like proteins described thus far in the literature, an absolute in vivo requirement for PrsA2 PPIase activity is evident in mouse infection models. This work illustrates the diversity of function associated with L. monocytogenes PrsA2 that serves to promote bacterial life within the infected host.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Female
  • Gene Expression Regulation, Bacterial
  • Humans
  • Listeria monocytogenes / chemistry
  • Listeria monocytogenes / enzymology*
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / pathogenicity*
  • Listeriosis / microbiology*
  • Mice
  • Molecular Conformation
  • Molecular Sequence Data
  • Peptidylprolyl Isomerase / chemistry
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Virulence

Substances

  • Peptidylprolyl Isomerase
  • PrsA2 protein, Listeria monocytogenes