Escherichia coli O157:H7 senses microbiota-produced riboflavin to increase its virulence in the gut

Abstract

Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic Escherichia coli (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system rbfSR , which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. rbfSR is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and Citrobacter rodentium , a surrogate for EHEC in mice. Introducing rbfSR into C. rodentium enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained rbfSR which has been kept in O157:H7 since then. Thus, acquiring rbfSR represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when rbfSR was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.

Z3495, a LysR-Type Transcriptional Regulator Encoded in O Island 97, Regulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli O157:H7

“…ChIP was performed as previously described with some modifications [ 21 , 22 ]. Inducible expression vectors carrying 3 × FLAG-tagged z3495 were constructed and transformed into the EHEC O157:H7 Δ z3495 .…”

L-Arabinose inhibits Shiga toxin type 2-converting bacteriophage induction in Escherichia coli O157:H7

“…E. coli O157:H7 intestinal colonization assay was conducted as the method previously described. 31 Briefly, seven-week-old male C57BL/6J mice (SPF Biotechnology Co., Ltd, Beijing, China) were orally administrated with 10 7 CFU E. coli O157:H7. The infected mice were anaesthetized and euthanized by cervical dislocation at day 3.…”

Genome and transcriptomic analysis of the adaptation of Escherichia coli to environmental stresses

“…Therefore, gaining rbfS/R is a significant step in the development of O157:H7. However, rbfS/R may eventually increase the pathogenicity of other EHEC serotypes [42] .…”