MarA, SoxS and Rob function as virulence factors in an Escherichia coli murine model of ascending pyelonephritis

Paul Casaz1, Lynne K Garrity-Ryan1, David McKenney1

  • 1Paratek Pharmaceuticals, Inc., 75 Kneeland Street, Boston, MA 02111, USA.

Insights

MarA, SoxS, and Rob transcription factors are crucial for Escherichia coli virulence in urinary tract infections. Deleting these factors significantly reduces bacterial infection severity in a mouse model.

Area of Science:

  • Microbiology and Molecular Biology
  • Bacterial Pathogenesis and Virulence Factors
  • Genetics and Gene Regulation

Background:

  • MarA, SoxS, and Rob are AraC family transcription factors historically linked to antibiotic resistance and stress tolerance.
  • Limited experimental data exist regarding their role in bacterial virulence regulation.

Purpose of the Study:

  • To investigate the role of MarA, SoxS, and Rob transcription factors in the virulence of *Escherichia coli*.
  • To assess the contribution of these factors in a clinically relevant model of urinary tract infection.

Main Methods:

  • Utilized a murine model of ascending pyelonephritis to study *E. coli* virulence.
  • Compared virulence of clinical isolates with isogenic strains lacking individual or all three transcription factors (marA, soxS, rob).
  • Performed complementation studies to confirm the role of each transcription factor.

Main Results:

  • Triple knockout strains lacking MarA, SoxS, and Rob were significantly less virulent than parental strains.
  • Complementation with individual factors restored wild-type virulence in the triple knockout.
  • Deletion of soxS or rob alone had a more detrimental effect on virulence than marA deletion.

Conclusions:

  • MarA, SoxS, and Rob transcription factors collectively contribute to *E. coli* virulence in vivo.
  • These factors play a significant role in the pathogenesis of urinary tract infections.

Related Concept Videos

Bacterial Gastroenteritis01:18

Bacterial Gastroenteritis

Bacterial gastroenteritis, characterized by diarrhea, abdominal cramps, and vomiting, is often caused by ingestion of contaminated food or water and is frequently associated with pathogenic Escherichia coli strains. These microbes exploit two principal mechanisms to inflict disease.Shiga toxin–producing E. coli, also referred to as STEC—notably O157:H7—release Shiga toxins that target ribosomes, blocking protein synthesis. The B subunit of the toxin binds the host glycolipid receptor...
Determinants of Bacterial Pathogenicity and Virulence01:20

Determinants of Bacterial Pathogenicity and Virulence

Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
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...
Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
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...
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,...