Phage therapy of Cronobacter-induced urinary tract infection in mice.

BACKGROUND: 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. MATERIAL/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Analysis of the DNA region mediating increased thermotolerance at 58°C in Cronobacter sp. and other enterobacterial strains.

Cronobacter spp. are opportunistic pathogens associated with serious infections in neonates. The increased stress tolerance, including thermoresistance, of some Cronobacter strains can promote their survival in production facilities and thus raise the possibility of contamination of dried infant milk formula, which has been identified as a potential source of infection. In this study, we characterized a DNA region which is present in some Cronobacter strains and which contributes to their prolonged survival at 58°C. The 18 kbp long region containing 22 open reading frames was sequenced in Cronobacter sakazakii ATCC 29544. The major feature of the region contained a cluster of conserved genes, most of them having significant homologies with bacterial proteins involved in some type of stress response, including heat, oxidation and acid stress. The same thermoresistance DNA region was detected in strains belonging to the genera Cronobacter, Enterobacter, Citrobacter and Escherichia and its presence positively correlated with increased thermotolerance.