ABSTARCT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a human pathogen that causes a variety of diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. Flagellum-dependent motility plays diverse roles in the pathogenesis of EHEC O157:H7, including its migration to an optimal host site, adherence and colonization, survival at the infection site, and post-infection dispersal. However, it is very expensive for cellular economy in terms of the number of genes and the energy required for flagellar biosynthesis and functioning. Furthermore, the flagellar filament bears strong antigenic properties that induce a strong host immune response. Consequently, the flagellar gene expression and biosynthesis are highly regulated to occur at the appropriate time and place by different regulatory influences. The present review focuses on the regulatory mechanisms of EHEC O157:H7 motility and flagellar biosynthesis, especially in terms of flagellar gene regulation by environmental factors, regulatory proteins, and small regulatory RNAs.

Sensing specific gut metabolites is an important strategy for inducing crucial virulence programs by enterohemorrhagic Escherichia coli (EHEC) O157:H7 during colonization and infection. Here, we identified a virulence-regulating pathway wherein the PhoQ/PhoP two-component regulatory system signals to the O island 119-encoded low magnesium-induced regulator A (LmiA), which, in turn, activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence in the low-magnesium conditions of the large intestine. This regulatory pathway is widely present in a range of EHEC and enteropathogenic E. coli (EPEC) serotypes. Disruption of this pathway significantly decreased EHEC O157:H7 adherence in the mouse intestinal tract. Moreover, mice fed a magnesium-rich diet showed significantly reduced EHEC O157:H7 adherence in vivo , indicating that magnesium may help in preventing EHEC and EPEC infection in humans.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a principally foodborne pathogen linked to serious diseases, including bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Comparative genomics analysis revealed that EHEC O157 contains 177 unique genomic islands, termed O islands, compared with the nonpathogenic E. coli K-12 laboratory strain. These O islands contribute largely to the pathogenicity of EHEC O157:H7 by providing numerous virulence factors, effectors, virulence regulatory proteins, and virulence regulatory sRNAs. The present review aimed to provide a comprehensive understanding of the research progress on the function of O islands, especially focusing on virulence-related O islands.

Salmonella is one of the most important enteric pathogens worldwide, which is able to cause lethal systemic infection via survival and replication in host macrophages. Lactate, a byproduct of anaerobic or aerobic glycolysis, can induce macrophage M2 polarization, but the relationship between lactate-mediated macrophage M2 polarization and bacterial infection is poorly understood. Here, we evaluated the role of lactate and lactate-mediated macrophage M2 polarization in the pathogenicity of Salmonella . We found that lactate levels were significantly increased in Salmonella -infected macrophages, and the increased lactate was derived from the host. Macrophage and mouse infection assays showed that the addition of lactate enhanced Salmonella replication within macrophages and the colonization of mouse systemic loci, while pharmacological or genetic inhibition of host lactate production impaired Salmonella intracellular replication and its virulence in mice. Further analysis revealed that lactate promotes M2 polarization of Salmonella -infected macrophages, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated Salmonella growth promotion. Moreover, we showed that macrophage-derived lactate induces the Salmonella pathogenicity island (SPI)-2 type III secretion system, leading to increased translocation of the SPI-2 effector SteE, which is responsible for driving M2 polarization. Overall, these findings suggest that lactate promotes Salmonella intracellular replication and systemic infection via driving macrophage M2 polarization and highlight the complex interactions between Salmonella and macrophages. IMPORTANCE: The important enteropathogen Salmonella can cause lethal systemic infection via survival and replication in host macrophages. Lactate represents an abundant intracellular metabolite during bacterial infection, which can also induce macrophage M2 polarization. In this study, we found that macrophage-derived lactate promotes the intracellular replication and systemic infection of Salmonella . During Salmonella infection, lactate via the Salmonella type III secretion system effector SteE promotes macrophage M2 polarization, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated Salmonella growth promotion. This study highlights the complex interactions between Salmonella and macrophages and provides an additional perspective on host-pathogen crosstalk at the metabolic interface.

Background: Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) causes bloody diarrhea and hemolytic-uremic syndrome. EHEC O157 encounters varied microenvironments during infection, and can efficiently adapt to these using the two-component system (TCS). Recently, a functional TCS, RstAB, has been implicated in the regulation of virulence of several bacterial pathogens. However, the regulatory function of RstAB in EHEC O157 is poorly understood. This study aimed at providing insights into the global effects of RstA on gene expression in EHEC O157. Results: In the present study, we analyzed gene expression differences between the EHEC O157 wild-type strain and a ΔrstA mutant using RNA-seq technology. Genes with differential expression in the ΔrstA mutant compared to that in the wild-type strain were identified and grouped into clusters of orthologous categories. RstA promoted EHEC O157 LEE gene expression, adhesion in vitro, and colonization in vivo by indirect regulation. We also found that RstA could bind directly to the promoter region of hdeA and yeaI to enhance acid tolerance and decrease biofilm formation by modulating the concentration of c-di-GMP. Conclusions: In summary, the RstAB TCS in EHEC O157 plays a major role in the regulation of virulence, acid tolerance, and biofilm formation. We clarified the regulatory function of RstA, providing an insight into mechanisms that may be potential drug targets for treatment of EHEC O157-related infections.