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

Tóthová L, Celec P, Bábíčková J, Gajdošová J, Al-Alami H, Kamodyova N, Drahovská H, Liptáková A, Turňa J, Hodosy J - Med. Sci. Monit. (2011)

Bottom Line: 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.Long-term effects and safety of the treatment are currently unknown.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.

ABSTRACT

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.

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Analysis of gene expression using real time PCR. * denotes p<0.05 vs. CTRL; ** denotes p<0.01 vs. CTRL; *** denotes p<0.05 vs. CRONO.
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f3-medscimonit-17-7-br173: Analysis of gene expression using real time PCR. * denotes p<0.05 vs. CTRL; ** denotes p<0.01 vs. CTRL; *** denotes p<0.05 vs. CRONO.

Mentions: Analysis of expression of TNF alpha and MCP-1 revealed that both cytokines were upregulated in the bladder of infected mice (TNF alpha by 72%; t=3.02; p=0.007; MCP-1 by 52%; t=3.03; p=0.007). These differences were reduced by phage therapy (TNF alpha by 35%; t=3.58; p=0.002; Figure 3C; MCP-1 by 22%; t=2.53; p=0.02; Figure 3D). In the renal cortex only the infection-induced increase in expression of MCP-1 was significant (by 48%; t=2.57; p=0.02; Figure 3B). The decrease due to phage therapy was significant for TNF alpha (by 36%; t=2.78; p=0.02; Figure 3A).


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

Tóthová L, Celec P, Bábíčková J, Gajdošová J, Al-Alami H, Kamodyova N, Drahovská H, Liptáková A, Turňa J, Hodosy J - Med. Sci. Monit. (2011)

Analysis of gene expression using real time PCR. * denotes p<0.05 vs. CTRL; ** denotes p<0.01 vs. CTRL; *** denotes p<0.05 vs. CRONO.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539570&req=5

f3-medscimonit-17-7-br173: Analysis of gene expression using real time PCR. * denotes p<0.05 vs. CTRL; ** denotes p<0.01 vs. CTRL; *** denotes p<0.05 vs. CRONO.
Mentions: Analysis of expression of TNF alpha and MCP-1 revealed that both cytokines were upregulated in the bladder of infected mice (TNF alpha by 72%; t=3.02; p=0.007; MCP-1 by 52%; t=3.03; p=0.007). These differences were reduced by phage therapy (TNF alpha by 35%; t=3.58; p=0.002; Figure 3C; MCP-1 by 22%; t=2.53; p=0.02; Figure 3D). In the renal cortex only the infection-induced increase in expression of MCP-1 was significant (by 48%; t=2.57; p=0.02; Figure 3B). The decrease due to phage therapy was significant for TNF alpha (by 36%; t=2.78; p=0.02; Figure 3A).

Bottom Line: 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.Long-term effects and safety of the treatment are currently unknown.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus