Salicylidene acylhydrazides that affect type III protein secretion in Salmonella enterica serovar typhimurium.

  • Negrea A
  • Bjur E
  • Ygberg S
 et al. 
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A collection of nine salicylidene acylhydrazide compounds were tested for their ability to inhibit the activity of virulence-associated type {III} secretion systems {(T3SSs)} in Salmonella enterica serovar Typhimurium. The compounds strongly affected Salmonella pathogenicity island 1 {(SPI1)} {T3SS-mediated} invasion of epithelial cells and in vitro secretion of {SPI1} invasion-associated effector proteins. The use of a {SPI1} effector beta-lactamase fusion protein implicated intracellular entrapment of the protein construct upon application of a salicylidene acylhydrazide, whereas the use of chromosomal transcriptional gene fusions revealed a compound-mediated transcriptional silencing of {SPI1.} Salicylidene acylhydrazides also affected intracellular bacterial replication in murine macrophage-like cells and blocked the transport of an epitope-tagged {SPI2} effector protein. Two of the compounds significantly inhibited bacterial motility and expression of extracellular flagellin. We conclude that salicylidene acylhydrazides affect bacterial {T3SS} activity in S. enterica and hence could be used as lead substances when designing specific inhibitors of bacterial {T3SSs} in order to pharmaceutically intervene with bacterial virulence.

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  • Aurel Negrea

  • Eva Bjur

  • Sofia Ygberg

  • Mikael Elofsson

  • Wolf-Watz Hans

  • Mikael Rhen

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