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Related Concept Videos

Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

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Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
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Global Regulatory Systems01:28

Global Regulatory Systems

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Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
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Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

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Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
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Constitutive and Regulated Gene Expression01:27

Constitutive and Regulated Gene Expression

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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

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Sporulation is a complex developmental process that allows certain Gram-positive bacteria, such as Bacillus subtilis and Clostridium species, to survive extreme environmental conditions. This process is tightly regulated by a series of signaling cascades and transcriptional controls, ensuring the formation of a highly resistant endospore.Sporulation is triggered by unfavorable conditions, such as nutrient depletion, and is governed by a phosphorelay system. One of the sensor kinases, such as...
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Stringent Response in E. coli01:23

Stringent Response in E. coli

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Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
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Complex Regulation of Gamma-Hemolysin Expression Impacts Staphylococcus aureus Virulence.

Mariane Pivard1, Isabelle Caldelari2, Virginie Brun3,4

  • 1CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.

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|June 22, 2023
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Summary

Staphylococcus aureus gamma-hemolysin CB (HlgCB) toxin levels vary significantly in pneumonia isolates due to genetic changes. A single 5' UTR SNP drastically impacts HlgC translation, affecting virulence.

Keywords:
Staphylococcus aureusgamma-hemolysin CBmRNA translationpneumoniarabbit modeltoxin regulation

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Staphylococcus aureus produces pore-forming toxins like gamma-hemolysin CB (HlgCB), targeting the C5a receptor.
  • HlgCB is similar to Panton-Valentine leucocidin (PVL) and contributes to community-acquired pneumonia (CAP) severity.
  • Variations in HlgCB expression exist among clinical isolates, impacting S. aureus virulence.

Purpose of the Study:

  • To investigate the molecular basis for HlgCB expression and protein production variations in S. aureus clinical strains.
  • To determine the impact of genetic variations on HlgCB levels and HlgC/HlgB ratios.
  • To correlate HlgCB levels with S. aureus virulence in a pneumonia model.

Main Methods:

  • Absolute quantification of HlgCB using mass spectrometry in 39 CAP isolates.
  • Analysis of hlgCB expression at promoter, mRNA processing, and translation levels.
  • Identification of single nucleotide polymorphisms (SNPs) in regulatory regions of hlgCB.
  • Assessment of HlgCB virulence in a rabbit pneumonia model.

Main Results:

  • Significant variations in HlgC and HlgB yields were observed between isolates, with dissociated levels in 10% of strains.
  • HlgCB level and HlgC/HlgB ratio depend on hlgC promoter activity, mRNA processing, and translation.
  • A single SNP in the 5' UTR of hlgCB mRNA strongly impaired HlgC translation in the USA300 strain.
  • High HlgCB levels correlated with mortality in a rabbit pneumonia model.

Conclusions:

  • Subtle genomic variations, particularly SNPs in noncoding regions, can significantly impact S. aureus HlgCB expression and virulence.
  • HlgCB plays a crucial role in S. aureus virulence in PVL-negative pneumonia strains.
  • Understanding these regulatory mechanisms is key to deciphering bacterial pathogenesis and developing targeted therapies.