Free Content Components of the peptidoglycan-recycling pathway modulate invasion and intracellular survival of Salmonella enterica serovar Typhimurium

Authors: Anders Folkesson1; Sofia Eriksson1; Mats Andersson1; James T. Park2; Staffan Normark1

Source: Cellular Microbiology, Volume 7, Number 1, January 2005 , pp. 147-155(9)

Publisher: Blackwell Publishing

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Abstract:

Summary

bgr-Lactam resistance in enteric bacteria is frequently caused by mutations in ampD encoding a cytosolic N-acetylmuramyl-l-alanine amidase. Such mutants are blocked in murein (peptidoglycan) recycling and accumulate cytoplasmic muropeptides that interact with the transcriptional activator ampR, which de-represses bgr-lactamase expression. Salmonella enterica serovar Typhimurium, an extensively studied enteric pathogen, was used to show that mutations in ampD decreased the ability of S. typhimurium to enter a macrophage derived cell line and made the bacteria more potent as inducers of inducible nitric oxide synthase (iNOS), as compared with the wild-type. ampG mutants, defective in the transport of recycled muropeptides across the cytoplasmic membrane, behaved essentially as the wild-type in invasion assays and in activation of iNOS. As ampD mutants also have reduced in vivo fitness in a murine model, we suggest that the cytoplasmic accumulation of muropeptides affects the virulence of the ampD mutants.

Document Type: Research article

DOI: 10.1111/j.1462-5822.2004.00443.x

Affiliations: 1: Mikrobiologiskt och Tumörbiologiskt Centrum, Karolinska Institutet, S-17177 Stockholm, Sverige, Sweden. 2: Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, USA.

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