Related Experiment Video

Updated: May 11, 2026

A Non-Coding Small RNA MicC Contributes to Virulence in Outer Membrane Proteins in Salmonella Enteritidis
06:30

A Non-Coding Small RNA MicC Contributes to Virulence in Outer Membrane Proteins in Salmonella Enteritidis

Published on: January 27, 2021

The lipopolysaccharide modification regulator PmrA limits Salmonella virulence by repressing the type three-secretion

Jeongjoon Choi1, Eduardo A Groisman

  • 1Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536-0812, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 22, 2013
PubMed

Insights

The Salmonella PmrA protein surprisingly enhances virulence by repressing the ssrB gene, which controls macrophage-killing systems. This finding reveals a novel antivirulence role for PmrA in Salmonella Typhimurium infections.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • Salmonella enterica serovar Typhimurium causes gastroenteritis and typhoid fever.
  • The regulatory protein PmrA controls lipopolysaccharide (LPS) modification genes.
  • PmrA-dependent LPS modifications are linked to resistance and Salmonella virulence.

Purpose of the Study:

  • To investigate the role of PmrA in Salmonella Typhimurium virulence.
  • To elucidate the regulatory mechanism by which PmrA influences virulence gene expression.
  • To understand the interaction between PmrA, ssrB, and the Spi/Ssa secretion system.

Main Methods:

  • Construction and phenotypic analysis of a pmrA null mutant in Salmonella Typhimurium.
  • In vivo virulence assays using intraperitoneal inoculation in C3H/HeN mice.
  • Reporter assays and gene expression analysis to study PmrA-SsrB interactions and downstream effects.
  • Site-directed mutagenesis of the ssrB promoter to assess PmrA binding and repression.

Main Results:

  • A pmrA null mutant exhibited significantly increased virulence (hypervirulence) in a mouse model.
  • PmrA was found to bind to the ssrB promoter and repress its transcription.
  • The pmrA mutant showed elevated expression of SsrB-dependent genes and enhanced macrophage killing.
  • Mutating the ssrB promoter to abolish PmrA repression resulted in hypervirulence comparable to the pmrA mutant.

Conclusions:

  • PmrA acts as an antivirulence factor by repressing the ssrB virulence gene.
  • This repression limits the acute phase of infection, potentially promoting pathogen persistence.
  • The PmrA-SsrB regulatory axis is critical for modulating Salmonella Typhimurium pathogenesis within host tissues.
Keywords:
Salmonella pathogenicity island 2cytotoxicity

More Related Videos

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages11:10

High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages

Published on: August 11, 2014

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues07:10

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues

Published on: February 19, 2019

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...
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...
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,...
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Gene Regulation During Sporulation01:17

Gene Regulation During Sporulation

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...