Phage therapy of Cronobacter-induced urinary tract infection in mice

Abstract

Cronobacter spp. is an opportunistic pathogen causing rare but dangerous cases of meningitis, sepsis and urinary tract infection. Phage therapy overcomes antibiotic resistance and represents an alternative approach to standard antimicrobial treatment. There are no published studies on the use of phages against Cronobacter spp. in vivo. The aim of our study was to prove the effects of isolated Cronobacter-specific phages on renal colonization in a model of urinary tract infection in mice.Urinary tract infection was induced by transurethral application of Cronobacter turicensis (1011 CFU/ml). Simultaneously, isolated Cronobacter-specific phages were administered intraperitoneally (1011 PFU/ml). After 24 hours, kidneys and bladder were collected and used for cultivation and analysis of gene expression and oxidative stress markers.Phage therapy reduced the number of Cronobacter colonies in the kidney by 70%. Higher levels of malondialdehyde were reduced by phage therapy without affecting the antioxidant status. The expression of pro-inflammatory cytokines tumor necrosis factor-alpha and monocyte chemoattractant protein-1 increased by the infection and was attenuated by phage therapy.Phage therapy proved effective in the prevention of ascending renal infection in a murine model of urinary tract infection. Long-term effects and safety of the treatment are currently unknown. Further studies should test phage therapy in other Cronobacter infection models.