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Epigenetic regulation of the nitrosative stress response and intracellular macrophage survival by extraintestinal pathogenic Escherichia coli.
Mol Microbiol. 2012 Mar; 83(5):908-25
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18 Jan 2012
New Finding
DOI: 10.3410/f.13477972.14858076
Bateman and Seed describe a molecular link between the regulation of type 1 fimbriae and the expression of tolerance to reactive nitrogen intermediates in extraintestinal pathogenic Escherichia coli (ExPEC). The discovery is interesting because it ties together the control of expression of an important...Continue reading
Bateman and Seed describe a molecular link between the regulation of type 1 fimbriae and the expression of tolerance to reactive nitrogen intermediates in extraintestinal pathogenic Escherichia coli (ExPEC). The discovery is interesting because it ties together the control of expression of an important adhesin and a stress response that can assist bacterial survival in macrophages.
The connection is provided by FimX, an integrase-like site-specific recombinase that can substitute for FimB and FimE, the recombinases that are native to the type 1 fimbrial locus. The authors report that, in addition to its role at the fim locus, FimX inverts a DNA fragment that carries the promoter of the hyxR gene, thought to encode a member of the LuxR-like response regulator family. The molecular dissection of the FimX-mediated DNA inversion mechanism at hyxR is still at an early stage, but it already shows important differences to the well-studied FimB- and FimE-mediated inversion of the type 1 fimbrial promoter. These include independence from the integration host factor (IHF) and H-NS architectural proteins. It will be very interesting to follow the development of the FimX-hyxR story in the future, not least because genetic switches that appear at first glance to operate randomly can sometimes reveal an element of directionality in their responses to specific environmental stimuli.
The connection is provided by FimX, an integrase-like site-specific recombinase that can substitute for FimB and FimE, the recombinases that are native to the type 1 fimbrial locus. The authors report that, in addition to its role at the fim locus, FimX inverts a DNA fragment that carries the promoter of the hyxR gene, thought to encode a member of the LuxR-like response regulator family. The molecular dissection of the FimX-mediated DNA inversion mechanism at hyxR is still at an early stage, but it already shows important differences to the well-studied FimB- and FimE-mediated inversion of the type 1 fimbrial promoter. These include independence from the integration host factor (IHF) and H-NS architectural proteins. It will be very interesting to follow the development of the FimX-hyxR story in the future, not least because genetic switches that appear at first glance to operate randomly can sometimes reveal an element of directionality in their responses to specific environmental stimuli.
Disclosures
None declared
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Dorman C: F1000Prime Recommendation of [Bateman SL and Seed PC, Mol Microbiol 2012, 83(5):908-25]. In F1000Prime, 18 Jan 2012; DOI: 10.3410/f.13477972.14858076. F1000Prime.com/13477972#eval14858076
F1000Prime Recommendations, Dissents and Comments for [Bateman SL and Seed PC, Mol Microbiol 2012, 83(5):908-25]. In F1000Prime, 22 May 2013; F1000Prime.com/13477972
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Extraintestinal pathogenic Escherichia coli (ExPEC) reside in the enteric tract as a commensal reservoir, but can transition to a pathogenic state by invading normally sterile niches, establishing infection, and disseminating to invasive sites like the bloodstream. Macrophages are required for ExPEC dissemination, suggesting the pathogen has developed mechanisms to persist within professional phagocytes. Here, we report that FimX, an ExPEC-associated DNA invertase that regulates the major virulence factor type 1 pili (T1P), is also an epigenetic regulator of a LuxR-like response regulator HyxR. FimX regulated hyxR expression through bidirectional phase inversion of its promoter region at sites different from the type 1 pili promoter and independent of integration host factor IHF. In vitro, transition from high to low HyxR expression produced enhanced tolerance of reactive nitrogen intermediates (RNI), primarily through de-repression of hmpA, encoding a nitric oxide detoxifying flavohemoglobin. However, in the macrophage, HyxR produced large effects on intracellular survival in the presence and absence of RNI and independent of Hmp. Collectively, we have shown that the ability of ExPEC to survive in macrophages is contingent upon the proper transition from high to low HyxR expression through epigenetic regulatory control by FimX.
© 2012 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2012.07977.x
PMID: 22221182
