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The regulation of pap and type 1 fimbriation in Escherichia coli
1Research School of Biosciences, University of Kent at Canterbury, Canterbury, Kent, CT2 7NJ, UK. I.C.Blomfield@ukc.ac.uk
Abstract:
The ability of bacterial pathogens to bind to the host mucosa is a critical step in the pathogenesis of many bacterial infections and, for Escherichia coli, a large number of different fimbrial adhesins have been implicated as virulence factors. In this chapter, our current understanding of the regulatory mechanisms that control the expression of two of the best characterized fimbrial adhesins, pyelonephritis-associated pilus (encoded by pap) and the type 1 fimbria (encoded by fim), will be described. The expression of both fimbrial adhesins is controlled by phase variation (the reversible and apparently random switching between expressing ('on') and non-expressing ('off') states), and is regulated in response to environmental conditions. The phase variation of pap (and of some other fimbriae in Escherichia coli) is determined by the formation of alternative nucleoprotein complexes that either activate (phase 'on') or suppress (phase 'off') transcription of the fimbria genes. Formation of each complex protects a single Dam methylation site (5' GATC) from modification (GATCdist in phase 'on' cells and GATCprox in phase 'off' cells). Furthermore, complex formation is inhibited by methylation of the two 5' GATC sites. Both the phase variation of pap and the transcription of the pap genes in phase 'on' cells, are regulated and expression is subject to both positive and negative feedback control. In contrast to pap, the phase variation of fim is determined by the site-specific inversion of a short element of DNA (the fim switch). In phase 'on' cells, a promoter within the invertible element directs the transcription of the fim structural genes, whereas in phase 'off' cells transcription of the fimbrial genes is silenced. Despite the very different molecular mechanisms controlling the expression of pap and fim, the two systems share many features in common and have probably evolved to fulfill the same function. In addition to details about the molecular mechanisms that control pap and fim, the possible physiological significance of the observed regulation will be discussed.
Insights
Escherichia coli uses two distinct mechanisms, nucleoprotein complexes for pap and DNA inversion for fim, to regulate fimbrial adhesin expression in response to environmental cues.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- Bacterial pathogens utilize fimbrial adhesins for host mucosa binding, a crucial step in infection.
- Escherichia coli employs various fimbrial adhesins as virulence factors.
- Understanding the regulation of these adhesins is key to combating bacterial infections.
Purpose of the Study:
- To describe the regulatory mechanisms controlling pyelonephritis-associated pilus (pap) and type 1 fimbria (fim) expression in Escherichia coli.
- To elucidate the role of phase variation in fimbrial adhesin regulation.
- To discuss the physiological significance of these regulatory systems.
Main Methods:
- Analysis of nucleoprotein complex formation regulating pap gene transcription.
- Investigation of Dam methylation site protection in phase variation.
- Examination of site-specific DNA inversion controlling fim gene expression.
Main Results:
- Pap phase variation involves alternative nucleoprotein complexes that protect Dam methylation sites.
- Fim phase variation is mediated by the inversion of a DNA element containing a promoter.
- Both systems exhibit regulation in response to environmental conditions and share common regulatory features.
Conclusions:
- Escherichia coli employs distinct molecular mechanisms (nucleoprotein complexes vs. DNA inversion) for regulating pap and fim fimbrial adhesin expression.
- Phase variation in both systems allows adaptation to environmental conditions.
- These regulatory strategies likely evolved to serve similar functional purposes in pathogenesis.
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