Uropathogenic Escherichia Coli Infection: Potential Importance of Epigenetics

Abstract

Patients suffering from recurrent urinary tract infections (UTIs) may be maintained on antibiotic prophylaxis, or even treated by surgery. However, there are no biological data on which to base such treatment selection for the individual patient. This highlights the need for a biological marker that might predict UTI recurrence risk. Infection of mammalian tissues with bacteria, viruses and other pathogens results in the modification of the host cell epigenome, particularly DNA methylation. We recently demonstrated that in vitro infection of bladder uroepithelial cells with uropathogenic Escherichia coli results in hypermethylation of the tumor suppressor gene CDKN2A, providing proof-of-concept that uropathogenic E. coli infection modulates the host cell epigenome. If postinfection persistence of UTI-induced uroepithelial DNA hypermethylation were to be associated with subsequent UTI propensity, these epigenetic marks could act as a potential biomarker for UTI recurrence risk and could be used to rationalize and improve treatment of patients with infection-associated uropathies.

KEYWORDS::

• bladder
• CDKN2A
• DNA methylation
• DNA methyltransferase
• Helicobacter pylori
• infection recurrence
• Schistosoma mansoni
• urinary tract infection
• uroepithelium
• uropathogenic Escherichia coli

Acknowledgements

The authors would like to thank A Kapila-Vincent for her contribution of conditioned medium and lipopolysaccharide data and help with Figure 1.

Financial & competing interests disclosure

This work is supported by a grant from the PSI foundation to C Tolg and DJ Bagli. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work is supported by a grant from the PSI foundation to C Tolg and DJ Bagli. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.