Abstract
AbstractPurposePseudomonas aeruginosakeratitis is a severe ocular infection that can lead to perforation of the cornea. In this study we evaluated the role of bacterial quorum sensing in generating corneal perforation and bacterial proliferation and tested whether co-injection of the predatory bacteriaBdellovibrio bacteriovoruscould alter the clinical outcome.P. aeruginosawithlasRmutations were observed among keratitis isolates from a study collecting samples from India, so an isogeniclasRmutant strain ofP. aeruginosawas included.MethodsRabbit corneas were intracorneally infected withP. aeruginosastrain PA14 or an isogenic ΔlasRmutant and co-injected with PBS orB. bacteriovorus. After 24 h, eyes were evaluated for clinical signs of infection. Samples were analyzed by scanning electron microscopy, optical coherence tomography, sectioned for histology, and corneas were homogenized for CFU enumeration and for inflammatory cytokines.ResultsWe observed that 54% of corneas infected by wild-type PA14 presented with a corneal perforation (n=24), whereas only 4% of PA14 infected corneas that were co-infected withB. bacteriovorusperforate (n=25). Wild-typeP. aeruginosaproliferation was reduced 7-fold in the predatory bacteria treated eyes. The ΔlasRmutant was less able to proliferate compared to the wild-type, but was largely unaffected byB. bacteriovorus.ConclusionThese studies indicate a role for bacterial quorum sensing in the ability ofP. aeruginosato proliferate and cause perforation of the rabbit cornea. Additionally, this study suggests that predatory bacteria can reduce the virulence ofP. aeruginosain an ocular prophylaxis model.
Publisher
Cold Spring Harbor Laboratory