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Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence

View Article: PubMed Central - PubMed

ABSTRACT

The biogeography of the gut is diverse in its longitudinal axis, as well as within specific microenvironments. Differential oxygenation and nutrient composition drive the membership of microbial communities in these habitats. Moreover, enteric pathogens can orchestrate further modifications to gain a competitive advantage toward host colonization. These pathogens are versatile and adept when exploiting the human colon. They expertly navigate complex environmental cues and interkingdom signaling to colonize and infect their hosts. Here we demonstrate how enterohemorrhagic Escherichia coli (EHEC) uses three sugar-sensing transcription factors, Cra, KdpE, and FusR, to exquisitely regulate the expression of virulence factors associated with its type III secretion system (T3SS) when exposed to various oxygen concentrations. We also explored the effect of mucin-derived nonpreferred carbon sources on EHEC growth and expression of virulence genes. Taken together, the results show that EHEC represses the expression of its T3SS when oxygen is absent, mimicking the largely anaerobic lumen, and activates its T3SS when oxygen is available through Cra. In addition, when EHEC senses mucin-derived sugars heavily present in the O-linked and N-linked glycans of the large intestine, virulence gene expression is initiated. Sugars derived from pectin, a complex plant polysaccharide digested in the large intestine, also increased virulence gene expression. Not only does EHEC sense host- and microbiota-derived interkingdom signals, it also uses oxygen availability and mucin-derived sugars liberated by the microbiota to stimulate expression of the T3SS. This precision in gene regulation allows EHEC to be an efficient pathogen with an extremely low infectious dose.

No MeSH data available.


Related in: MedlinePlus

LEE gene expression in deletion strains under gluconeogenic, microaerobic conditions. (A) Expression of representative LEE genes by strains grown microaerobically in low-glucose DMEM. (B) Western blot assay of EspB secreted from strains grown microaerobically in low-glucose DMEM. Significance was assessed with Student’s t test. BSA, bovine serum albumin.
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fig7: LEE gene expression in deletion strains under gluconeogenic, microaerobic conditions. (A) Expression of representative LEE genes by strains grown microaerobically in low-glucose DMEM. (B) Western blot assay of EspB secreted from strains grown microaerobically in low-glucose DMEM. Significance was assessed with Student’s t test. BSA, bovine serum albumin.

Mentions: When we grew WT EHEC and all of the mutants under microaerobic conditions (the oxygen concentration was measured under microaerobic and aerobic conditions [see Fig. S5 in the supplemental material]), we saw the strong repressor and activator phenotypes become ameliorated, except in the ΔfusR ΔkdpE Δcra strain (Fig. 7A). Secretion of EspB was not significantly different from that of the WT either (Fig. 7B). Overall, these data indicate that the presence or lack of oxygen significantly alters how EHEC regulates LEE gene expression through Cra, KdpE, and FusR.


Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence
LEE gene expression in deletion strains under gluconeogenic, microaerobic conditions. (A) Expression of representative LEE genes by strains grown microaerobically in low-glucose DMEM. (B) Western blot assay of EspB secreted from strains grown microaerobically in low-glucose DMEM. Significance was assessed with Student’s t test. BSA, bovine serum albumin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120142&req=5

fig7: LEE gene expression in deletion strains under gluconeogenic, microaerobic conditions. (A) Expression of representative LEE genes by strains grown microaerobically in low-glucose DMEM. (B) Western blot assay of EspB secreted from strains grown microaerobically in low-glucose DMEM. Significance was assessed with Student’s t test. BSA, bovine serum albumin.
Mentions: When we grew WT EHEC and all of the mutants under microaerobic conditions (the oxygen concentration was measured under microaerobic and aerobic conditions [see Fig. S5 in the supplemental material]), we saw the strong repressor and activator phenotypes become ameliorated, except in the ΔfusR ΔkdpE Δcra strain (Fig. 7A). Secretion of EspB was not significantly different from that of the WT either (Fig. 7B). Overall, these data indicate that the presence or lack of oxygen significantly alters how EHEC regulates LEE gene expression through Cra, KdpE, and FusR.

View Article: PubMed Central - PubMed

ABSTRACT

The biogeography of the gut is diverse in its longitudinal axis, as well as within specific microenvironments. Differential oxygenation and nutrient composition drive the membership of microbial communities in these habitats. Moreover, enteric pathogens can orchestrate further modifications to gain a competitive advantage toward host colonization. These pathogens are versatile and adept when exploiting the human colon. They expertly navigate complex environmental cues and interkingdom signaling to colonize and infect their hosts. Here we demonstrate how enterohemorrhagic Escherichia coli (EHEC) uses three sugar-sensing transcription factors, Cra, KdpE, and FusR, to exquisitely regulate the expression of virulence factors associated with its type III secretion system (T3SS) when exposed to various oxygen concentrations. We also explored the effect of mucin-derived nonpreferred carbon sources on EHEC growth and expression of virulence genes. Taken together, the results show that EHEC represses the expression of its T3SS when oxygen is absent, mimicking the largely anaerobic lumen, and activates its T3SS when oxygen is available through Cra. In addition, when EHEC senses mucin-derived sugars heavily present in the O-linked and N-linked glycans of the large intestine, virulence gene expression is initiated. Sugars derived from pectin, a complex plant polysaccharide digested in the large intestine, also increased virulence gene expression. Not only does EHEC sense host- and microbiota-derived interkingdom signals, it also uses oxygen availability and mucin-derived sugars liberated by the microbiota to stimulate expression of the T3SS. This precision in gene regulation allows EHEC to be an efficient pathogen with an extremely low infectious dose.

No MeSH data available.


Related in: MedlinePlus