A new piece of the shigella pathogenicity puzzle: Spermidine accumulationby silencing of the speg gene

Marialuisa Barbagallo, Maria Letizia Di Martino, Lucia Marcocci, Paola Pietrangeli, Elena de Carolis, Mariassunta Casalino, Bianca Colonna, Gianni Prosseda

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The genome of Shigella, a gram negative bacterium which is the causative agent of bacillary dysentery, shares strong homologies with that of its commensal ancestor, Escherichia coli. The acquisition, by lateral gene transfer, of a large plasmid carrying virulence determinants has been a crucial event in the evolution towards the pathogenic lifestyle and has been paralleled by the occurrence of mutations affecting genes, which negatively interfere with the expression of virulence factors. In this context, we have analysed to what extent the presence of the plasmid-encoded virF gene, the major activator of the Shigella regulon for invasive phenotype, has modified the transcriptional profile of E. coli. Combining results from transcriptome assays and comparative genome analyses we show that in E. coli VirF, besides being able to up-regulate several chromosomal genes, which potentially influence bacterial fitness within the host, also activates genes which have been lost by Shigella. We have focused our attention on the speG gene, which encodes spermidine acetyltransferase, an enzyme catalysing the conversion of spermidine into the physiologically inert acetylspermidine, since recent evidence stresses the involvement of polyamines in microbial pathogenesis. Through identification of diverse mutations, which prevent expression of a functional SpeG protein, we show that the speG gene has been silenced by convergent evolution and that its inactivation causes the marked increase of intracellular spermidine in all Shigella spp. This enhances the survival of Shigella under oxidative stress and allows it to better face the adverse conditions it encounters inside macrophage. This is supported by the outcome of infection assays performed in mouse peritoneal macrophages and of a competitive-infection assay on J774 macrophage cell culture. Our observations fully support the pathoadaptive nature of speG inactivation in Shigella and reveal that the accumulation of spermidine is a key determinant in the pathogenicity strategy adopted by this microrganism.

Original languageEnglish
Article numbere27226
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 10 2011

Fingerprint

Shigella
Spermidine
Gene Silencing
spermidine
gene silencing
Virulence
pathogenicity
Genes
Macrophages
macrophages
Escherichia coli
genes
Assays
plasmids
inactivation
Plasmids
assays
virulence
Genome
Bacillary Dysentery

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Barbagallo, M., Di Martino, M. L., Marcocci, L., Pietrangeli, P., de Carolis, E., Casalino, M., ... Prosseda, G. (2011). A new piece of the shigella pathogenicity puzzle: Spermidine accumulationby silencing of the speg gene. PLoS One, 6(11), [e27226]. https://doi.org/10.1371/journal.pone.0027226

A new piece of the shigella pathogenicity puzzle : Spermidine accumulationby silencing of the speg gene. / Barbagallo, Marialuisa; Di Martino, Maria Letizia; Marcocci, Lucia; Pietrangeli, Paola; de Carolis, Elena; Casalino, Mariassunta; Colonna, Bianca; Prosseda, Gianni.

In: PLoS One, Vol. 6, No. 11, e27226, 10.11.2011.

Research output: Contribution to journalArticle

Barbagallo, M, Di Martino, ML, Marcocci, L, Pietrangeli, P, de Carolis, E, Casalino, M, Colonna, B & Prosseda, G 2011, 'A new piece of the shigella pathogenicity puzzle: Spermidine accumulationby silencing of the speg gene', PLoS One, vol. 6, no. 11, e27226. https://doi.org/10.1371/journal.pone.0027226
Barbagallo M, Di Martino ML, Marcocci L, Pietrangeli P, de Carolis E, Casalino M et al. A new piece of the shigella pathogenicity puzzle: Spermidine accumulationby silencing of the speg gene. PLoS One. 2011 Nov 10;6(11). e27226. https://doi.org/10.1371/journal.pone.0027226
Barbagallo, Marialuisa ; Di Martino, Maria Letizia ; Marcocci, Lucia ; Pietrangeli, Paola ; de Carolis, Elena ; Casalino, Mariassunta ; Colonna, Bianca ; Prosseda, Gianni. / A new piece of the shigella pathogenicity puzzle : Spermidine accumulationby silencing of the speg gene. In: PLoS One. 2011 ; Vol. 6, No. 11.
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