Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica

doi:10.1073/pnas.132047099

Polynucleotide phosphorylase is a global regulator of virulence and persistency in Salmonella enterica

^*Microbiology and Tumor Biology Center, Karolinska Institute, Nobels Väg 16, 171 77 Stockholm, Sweden; ^†Wolfson Institute for Biomedical Research, University College, London WC1E 6BT, United Kingdom; ^‡Molecular Microbiology Group, Institute of Food Research, Norwich Research Park, Colney, Norwich, NR4 7UA, United Kingdom; and ^§Swedish Institute for Infectious Disease Control, Nobels Väg 18, 171 82 Solna, Sweden

Edited by Stanley N. Cohen, Stanford University School of Medicine, Stanford, CA, and approved May 2, 2002 (received for review January 28, 2002)

Abstract

For many pathogens, the ability to regulate their replication in host cells is a key element in establishing persistency. Here, we identified a single point mutation in the gene for polynucleotide phosphorylase (PNPase) as a factor affecting bacterial invasion and intracellular replication, and which determines the alternation between acute or persistent infection in a mouse model for Salmonella enterica infection. In parallel, with microarray analysis, PNPase was found to affect the mRNA levels of a subset of virulence genes, in particular those contained in Salmonella pathogenicity islands 1 and 2. The results demonstrate a connection between PNPase and Salmonella virulence and show that alterations in PNPase activity could represent a strategy for the establishment of persistency.

Footnotes

↵ ¶ To whom reprint requests should be addressed. E-mail: mikael.rhen{at}mtc.ki.se.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF399929).
Abbreviations:

PNPase,

polynucleotide phosphorylase;

SPI,

Salmonella pathogenicity island;

CDS,

coding genes;

MDCK,

Madin–Darby canine kidney