Regulation of type VI secretion system during Burkholderia pseudomallei infection

Yahua Chen1, Jocelyn Wong, Guang Wen Sun

  • 1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.

Insights

The study reveals how Burkholderia pseudomallei controls its secretion systems. VirAG and BprC are essential regulators for the type VI secretion system (T6SS-1) in both lab conditions and host infections.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Type III and type VI secretion systems (T3SSs and T6SSs) are key virulence factors in Gram-negative bacteria.
  • In Burkholderia pseudomallei, T3SS-3 and T6SS-1 contribute significantly to virulence in mammalian hosts.

Purpose of the Study:

  • To elucidate the regulatory cascade controlling T3SS-3 and T6SS-1 expression in Burkholderia pseudomallei.
  • To investigate the roles of BsaN, VirAG, and BprC in regulating T6SS-1.

Main Methods:

  • Analysis of gene expression under different growth conditions (in vitro vs. host cells).
  • Identification of transcriptional start sites regulated by VirAG and BprC.
  • Assessment of bacterial virulence in macrophages and mouse models using regulator mutants.

Main Results:

  • BsaN regulates T3SS-3 effectors and T6SS-1 regulators (VirAG, BprC).
  • T6SS-1 expression is BprC-dependent in vitro, but VirAG-dependent in host cells (except for tssAB operon, which is BprC-dependent).
  • VirAG and BprC directly control T6SS-1 gene expression and are critical for virulence in macrophages and mice.

Conclusions:

  • VirAG and BprC are indispensable regulators for T6SS-1 function and Burkholderia pseudomallei virulence.
  • The regulatory mechanism differs between in vitro and host cell environments, highlighting adaptive virulence strategies.

Related Concept Videos

Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
Gram-negative Bacterial Protein Secretion Systems01:17

Gram-negative Bacterial Protein Secretion Systems

Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

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,...
Stringent Response in E. coli01:23

Stringent Response in E. coli

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...
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
Bacterial Translocation and Protein Secretion01:26

Bacterial Translocation and Protein Secretion

Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...