pap operon in Uropathogenic Escherichia coli
March 26th, 2008 ecoliSo I’m giving a journal club presentation in about an hour (as of 6, when I started this) and I figured I’d write a quick blog post about it.
The urinary tract is a multi-organ system that opens to the external environment and, as a result is prone to infections from various pathogens. Approximately 50% of women will get at least one urinary tract infection (UTI) in their lifetime. Uropathogenic Escherichia coli (UPEC) is responsible for 80% of community acquired UTIs, so it is an important pathogen to study.
There are essentially four stages in the current UTI model. Attachment of UPEC to the walls of the urinary tract, invasion of host epithelial cells, replication within those cells, and exfoliation of the epithelial cells concurrunt with bacterial efflux.
My presentation is primarily concerned with the first stage of this process, namely attachment or adherence. UPEC adhesion to the cell wall is absolutely required for initiation of infection, which makes adhesins molecules attractive candidates to study, for the ultimate purpose of vaccine creation. In addition to initiating infection, adherence prevents mictruition, or the ‘washing out’ of UPEC by urine flow throughout the urinary tract. Another important factor is that these adhesin proteins can act as surface antigens and be recognized by the host immune system.
Evading immune response would then become a primary ‘goal’ of UPEC, from selection pressures from the immune system. There are several homologous types of adhesins, and each has various roles in the infection process. In a multi organ system, a bacteria may want to express different adhesins at different times. This would help the organism adapt to microenvironments and conserve resources by limiting coexpression. In addition this could help UPEC evade host immune response by ‘hiding’ key surface antigens. This is known as phase variation.
I’m primarily concerned with a specific adhesin known as pyelonephritis-associated pili (Pap). These pili bind to uroepithelial cells and are responsible for symptomatic UTIs. The expression is controlled by a single operon (promoter, operator, structural gene sequences). UPEC contain several homologous copies of this operon, which have variation in their function.
So, we know that phase variation can control the expression of analogous adhesins, because the gene expression is regulated by different mechanisms. But, homologous copies of the pap operon are controlled by the same mechanism, even though they can have slightly different functions. How can a bacterium control the expression of these different pap operons?
The answer lies in the their very sequence variation. Sequence variation in the genes that encode their epigenetic regulators is selected for. These variation changes the functioning of the epigenetic proteins so that the expression can be modulated or the gene activators turned off. The expression of some copies of the operon are favored, and this is selected for by the host immune system.
References:
Makrina Totsika, Scott A. Beatson, Nicola Holden, David L. Gally (2008) Regulatory interplay between pap operons in uropathogenic Escherichia coli , Molecular Microbiology 67 (5) , 996–1011
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