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Infection and Immunity, July 2009, p. 2612-2623, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00280-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Posttranslocation Chaperone PrsA2 Contributes to Multiple Facets of Listeria monocytogenes Pathogenesis{triangledown} ,{dagger}

Francis Alonzo III,1 Gary C. Port,2,3,{ddagger} Min Cao,4 and Nancy E. Freitag1,2,3*

Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois,1 Seattle Biomedical Research Institute, Seattle, Washington,2 Molecular and Cellular Biology Program, University of Washington, Seattle, Washington,3 Department of Biological Sciences, Clemson University, Clemson, South Carolina4

Received 10 March 2009/ Returned for modification 17 April 2009/ Accepted 3 May 2009

Listeria monocytogenes is an intracellular bacterial pathogen whose virulence depends on the regulated expression of numerous secreted bacterial factors. As for other gram-positive bacteria, many proteins secreted by L. monocytogenes are translocated across the bacterial membrane in an unfolded state to the compartment existing between the membrane and the cell wall. This compartment presents a challenging environment for protein folding due to its high density of negative charge, high concentrations of cations, and low pH. We recently identified PrsA2 as a gene product required for L. monocytogenes virulence. PrsA2 was identified based on its increased secretion by strains containing a mutationally activated form of prfA, the key regulator of L. monocytogenes virulence gene expression. The prsA2 gene product is one of at least two predicted peptidyl-prolyl cis/trans-isomerases encoded by L. monocytogenes; these proteins function as posttranslocation protein chaperones and/or foldases. In this study, we demonstrate that PrsA2 plays a unique and important role in L. monocytogenes pathogenesis by promoting the activity and stability of at least two critical secreted virulence factors: listeriolysin O (LLO) and a broad-specificity phospholipase. Loss of PrsA2 activity severely attenuated virulence in mice and impaired bacterial cell-to-cell spread in host cells. In contrast, mutants lacking prsA1 resembled wild-type bacteria with respect to intracellular growth and cell-to-cell spread as well as virulence in mice. PrsA2 is thus distinct from PrsA1 in its unique requirement for the stability and full activity of L. monocytogenes-secreted factors that contribute to host infection.

* Corresponding author. Mailing address: UIC Department of Microbiology and Immunology (MC790), 835 S Wolcott Ave., Chicago, IL 60612-7344. Phone: (312) 355-4903. Fax: (312) 996-6415. E-mail: nfreitag{at}uic.edu

{triangledown} Published ahead of print on 18 May 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

{ddagger} Present address: Department of Molecular Microbiology, Washington University, St. Louis, MO 63110.

Infection and Immunity, July 2009, p. 2612-2623, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00280-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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