Current Research
Pediatric Enteropathogenic Pseudomonas aeruginosa
(PEPPA, aka Shanghai Fever)
Mentored by Alan Hauser, and in collaboration with Marine Lebrun Corbin, Sophie Nozick, Nathan Pincus, Jon Allen, Egon Ozer, and Cheng-Hsun Chiu
Pseudomonas aeruginosa (PA) is a Gram-negative bacterium and common cause of ventilator-associated pneumonia (VAP), bloodstream, wound, and urinary tract infections. High-risk populations include hospitalized patients with underlying disease, immunosuppression, or prior antibiotic treatment. Shanghai Fever (SF), first described in Asia, is a rare PA infection affecting previously healthy children who present with diarrhea, fever, and PA-positive blood cultures. It is hypothesized that SF results from oral ingestion of PA, enabling gastrointestinal infection and subsequent systemic spread. Despite its rarity, SF has an estimated mortality up to 89% due to the rapid progression of sepsis and severe complications, including ecthyma gangrenosum, meningitis, and shock.
Because of the aggressive progression of infection in patients with SF, we investigated whether PA strains causing this illness differed from strains causing typical bloodstream infections. Bloodstream isolates from SF patients were compared to isolates from typical bacteremia (non-SF isolates) in a mouse bacteremia model. As a group, SF isolates were significantly more virulent. One SF isolate was tested in a mouse pneumonia model and found to have the highest level of virulence among our extensive strain collection. Whole-genome phylogenetic analysis revealed that SF isolates are not monophyletic but belong to both of the two main phylogenetic clades of PA.
Given that a major PA virulence factor is the type III secretion system (T3SS), we hypothesized that SF isolates exhibit unusually high expression of the T3SS effector genes exoU and exoS. We performed qRT-PCR to measure exoU and exoS transcript abundance in SF versus non-SF isolates. While testing is ongoing, preliminary results suggest that exoU+ SF strains produce significantly (p = 0.015) more exoU transcript than exoU+ non-SF isolates. These findings suggest that enhanced T3SS expression of exoU could underlie the rapid disease progression and exceptional virulence of some SF strains.