Proteomic analysis of uropathogenic Escherichia coli

Abstract

Urinary tract infections (UTIs) are among the most common of bacterial infections in humans. Although a number of Gram-negative bacteria can cause UTIs, most cases are due to infection by uropathogenic E. coli (UPEC). Genomic studies have shown that UPEC encode a number of specialized activities that allow the bacteria to initiate and maintain infections in the environment of the urinary tract. Proteomic analyses have complemented the genomic data and have documented differential patterns of protein synthesis for bacteria growing ex vivo in human urine or recovered directly from the urinary tracts of infected mice. These studies provide valuable insights into the molecular basis of UPEC pathogenesis and have aided the identification of putative vaccine targets. Despite the substantial progress that has been achieved, many future challenges remain in the application of proteomics to provide a comprehensive view of bacterial pathogenesis in both acute and chronic UTIs.

Keywords::

• bacterial pathogenesis
• Escherichia coli
• microbial vaccines
• proteomics
• urinary tract infections
• uropathogenic Escherichia coli

Financial & competing interests disclosure

Work in the author's laboratory is funded in part by a grant from NHS (Grampian) Research Endowment Fund. The author has 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

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

Key issues

• Urinary tract infections (UTIs) are a major healthcare problem and a potential financial burden to the health service.

• The primary cause of UTIs is Escherichia coli.

• The specific strains of E. coli responsible for UTIs are known as uropathogenic E. coli (UPEC) and show a number of specific adaptations to allow them to grow in the urinary tract.

• Extensive genomic sequence data are available that highlight the distinct features UPEC from E. coli strains that cause gastrointestinal infections.

• Although much information can be drawn from genomic analyses, the use of proteomics has improved our knowledge of this important pathogen.

• Differential patterns of protein synthesis can be demonstrated for bacteria grown in urine ex vivo or recovered directly from the urinary tract of infected individuals.

• Based on proteomic analyses, there is no single variant of UPEC in circulation.

• Potential subunit vaccine targets have been identified through proteomic and genomic analyses. These are primarily derived from the outer membrane proteins.

• Although significant progress has been made, there are still challenges to be met in understanding the development of recurrent and chronic UTIs by E. coli.