Chicken IgY reduces the risk of Pseudomonas aeruginosa urinary tract infections in a murine model

Abstract

IntroductionUrinary tract infections (UTIs) withPseudomonas aeruginosaare a severe problem in disposed patients in modern healthcare.Pseudomonas aeruginosaestablishes recalcitrant biofilm infections and can develop antibiotic resistance. Gargling with avian egg yolk anti-Pseudomonasantibodies (IgY) has shown clinical effect in preventing onset of chronicP. aeruginosalung infections in patients with cystic fibrosis (CF). Therefore, we speculated whether passive intravesically administered IgY immunotherapy could be a novel strategy againstP. aeruginosaUTIs.AimTo evaluate if prophylactic repurposing of anti-PseudomonasIgY can prevent UTIs withP. aeruginosain a UTI mouse model.Materials and methodsIn vitro,P. aeruginosa(PAO1 and PAO3) was mixed with increasing concentrations of specific anti-PseudomonasIgY (sIgY) or non-specific control IgY (cIgY) and/or freshly isolated human neutrophils. Bacterial growth was evaluated by the optical density at 600 nm.In vivo,viaa temporary transurethral catheter, 10-week-old female Balb/c mice were intravesically infected with 50 ml of a bacterial suspension and sIgY, cIgY, or isotonic NaCl. IgY and NaCl were either co-instilled with the bacteria, or instilled prophylactically, 30 min prior to infection. The animals were euthanized 20 h after infection. Vesical bacteriology was quantified, and cytokine expression in the bladder homogenate was measured by multiplex cytokine assay.ResultsIn vitro, sIgY concentrations above 2.5% reduced bacterial growth in a dose-dependent manner.In vivo, a UTI lasting for minimum 7 days was established by installing 5 × 106colony-forming units (CFU) ofP. aeruginosaPAO1. sIgY reduced vesical bacterial load if co-installed withP. aeruginosaPAO1. Prophylactic sIgY and cIgY reduced bacterial load when compared to isotonic NaCl. CXCL2 and G-CSF were both increased in infected bladders compared to non-infected controls which had non-detectable levels. Co-installation of sIgY and bacteria nearly completely inhibited the inflammatory response. However, the cytokine levels in the bladder did not change after prophylactic administration of sIgY or cIgY.ConclusionProphylactic sIgY significantly reduces the amount of bacteria in the bladder in a mouse model ofP. aeruginosacystitis and may serve as a novel non-antibiotic strategy in preventingP. aeruginosaUTIs.