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Shigella flexneri Diguanylate Cyclases Regulate Virulence.

Ruchi Ojha1, Ashley A Dittmar1, Geoffrey B Severin2

  • 1Department of Biological Sciences, Western Michigan Universitygrid.268187.2, Kalamazoo, Michigan, USA.

Journal of Bacteriology
|September 20, 2021
PubMed
Summary
This summary is machine-generated.

Shigella flexneri virulence is regulated by cyclic di-GMP (c-di-GMP). Manipulating c-di-GMP levels affects biofilm formation, host cell invasion, and acid resistance in this pathogen.

Keywords:
Shigellabiofilmc-di-GMPcell-cell spreaddiguanylate cyclaseintracellular pathogeninvasion

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Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Shigella flexneri causes dysentery, a significant global health concern with rising antimicrobial resistance.
  • The role of cyclic di-GMP (c-di-GMP) signaling in S. flexneri virulence has not been previously investigated.
  • c-di-GMP is a crucial second messenger regulating bacterial behavior in response to environmental cues.

Purpose of the Study:

  • To investigate the role of c-di-GMP signaling in regulating S. flexneri virulence phenotypes.
  • To determine if manipulating c-di-GMP levels impacts biofilm formation, acid resistance, and host cell invasion.
  • To explore the impact of c-di-GMP on the S. flexneri transcriptome.

Main Methods:

  • Expression of a constitutively active diguanylate cyclase (VCA0956) from Vibrio cholerae in S. flexneri.
  • Measurement of intracellular c-di-GMP levels.
  • Assessment of biofilm formation, acid resistance, host cell invasion, and plaque size.
  • Transcriptomic analysis of S. flexneri expressing VCA0956.
  • Generation and analysis of S. flexneri diguanylate cyclase mutants.

Main Results:

  • Increased c-di-GMP levels in S. flexneri led to enhanced biofilm formation.
  • Elevated c-di-GMP correlated with reduced acid resistance, host cell invasion, and plaque size.
  • Transcriptomic analysis revealed repression of acid resistance genes.
  • S. flexneri DGC mutants showed reduced biofilm formation and host cell invasion, with increased acid resistance.

Conclusions:

  • c-di-GMP signaling plays a critical role in regulating key virulence behaviors of Shigella flexneri.
  • Modulation of c-di-GMP synthesis or degradation impacts S. flexneri's ability to cause disease.
  • Understanding c-di-GMP regulation offers potential targets for therapeutic interventions against shigellosis.