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Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence

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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 WT EHEC under different oxygen tensions. Expression of representative LEE genes by WT EHEC grown anaerobically, microaerobically, or aerobically in low-glucose DMEM with or without 1 mM pyruvate. Significance was assessed with Student’s t test.
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fig5: LEE gene expression in WT EHEC under different oxygen tensions. Expression of representative LEE genes by WT EHEC grown anaerobically, microaerobically, or aerobically in low-glucose DMEM with or without 1 mM pyruvate. Significance was assessed with Student’s t test.

Mentions: In addition to the roles of pyruvate and sugar sources in LEE gene expression, oxygen availability in the gut varies from luminal to the epithelial surface (46, 47). We next asked if LEE gene transcription would be altered under anaerobic or microaerobic conditions. The intestinal lumen, the first site encountered by EHEC, is predominantly anaerobic (46, 47). As fewer bacteria are present near the epithelial apical surfaces, oxygen can diffuse across the enterocytes, creating a microaerobic environment (47). Recently, it was shown that the microbiota can also affect oxygen availability in the gut (48, 49). Moreover, Citrobacter rodentium (extensively used as a surrogate EHEC model for murine infections [50]), triggers colonic hyperplasia through the activity of the LEE-encoded T3SS, increasing oxygenation at the mucosal surface, leading to the aerobic expansion of C. rodentium (6). EHEC and C. rodentium intimately attach to enterocytes in an environment that may change from microaerobic to aerobic. The expression of the LEE eae and espA genes is lower under anaerobic conditions (growth in an anaerobic chamber), while it is enhanced under aerobic conditions and reaches even higher levels under aerobic conditions in the presence of pyruvate (Fig. 5).


Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence
LEE gene expression in WT EHEC under different oxygen tensions. Expression of representative LEE genes by WT EHEC grown anaerobically, microaerobically, or aerobically in low-glucose DMEM with or without 1 mM pyruvate. Significance was assessed with Student’s t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: LEE gene expression in WT EHEC under different oxygen tensions. Expression of representative LEE genes by WT EHEC grown anaerobically, microaerobically, or aerobically in low-glucose DMEM with or without 1 mM pyruvate. Significance was assessed with Student’s t test.
Mentions: In addition to the roles of pyruvate and sugar sources in LEE gene expression, oxygen availability in the gut varies from luminal to the epithelial surface (46, 47). We next asked if LEE gene transcription would be altered under anaerobic or microaerobic conditions. The intestinal lumen, the first site encountered by EHEC, is predominantly anaerobic (46, 47). As fewer bacteria are present near the epithelial apical surfaces, oxygen can diffuse across the enterocytes, creating a microaerobic environment (47). Recently, it was shown that the microbiota can also affect oxygen availability in the gut (48, 49). Moreover, Citrobacter rodentium (extensively used as a surrogate EHEC model for murine infections [50]), triggers colonic hyperplasia through the activity of the LEE-encoded T3SS, increasing oxygenation at the mucosal surface, leading to the aerobic expansion of C. rodentium (6). EHEC and C. rodentium intimately attach to enterocytes in an environment that may change from microaerobic to aerobic. The expression of the LEE eae and espA genes is lower under anaerobic conditions (growth in an anaerobic chamber), while it is enhanced under aerobic conditions and reaches even higher levels under aerobic conditions in the presence of pyruvate (Fig. 5).

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