<p>(A) Schematic diagram showing that the integrated Shiga toxin prophage represses type III secretion (T3S) by restricting Ler-mediated LEE promoter activation. Under the conditions shown there is no expression of the PchA/B regulators associated with other integrated prophages that express effector proteins secreted by the T3S system. (B) Repression is overridden by the activity of activators such as PchA/B that are induced following sensing of niche specific signals in the animal host. A number of environmental signals are known to control T3S <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Tree1" target="_blank">[13]</a> including quorum sensing <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Sperandio1" target="_blank">[63]</a> which is proposed to contribute to the tropism of EHEC O157 for the terminal rectum of cattle <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Naylor1" target="_blank">[43]</a>. However, much less is known about whether these can act through Pch activation. PchA/B stimulate LEE1 and Ler expression leading to production of the T3S apparatus and secretion of LEE-encoded regulators, indicated as blue circles marked ‘LEE’ in the figure. (C) Psr regulators on effector-encoding prophages increase <i>gadE</i> expression leading to repression of LEE-encoded effector protein secretion. It is proposed that this prophage regulation allows non-LEE encoded effectors (Nle) to compete for export through the T3S system <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Tree2" target="_blank">[14]</a>. (D) A model for EHEC interaction with the epithelium. SOS stress responses result in prophage induction and Stx release in a subset of the population. Potentially certain stresses associated with the interaction with epithelial cells may induce this response. The released toxin induces the expression and redistribution of receptors to the epithelial cell surface <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Robinson1" target="_blank">[32]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Liu1" target="_blank">[62]</a>. T3S is repressed but can be induced by Pch regulators <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Abe1" target="_blank">[12]</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Tree1" target="_blank">[13]</a>, RgdR <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Flockhart1" target="_blank">[15]</a> and further controlled by PsrA/B <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Tree2" target="_blank">[14]</a> present on cryptic prophages to ensure co-ordinate T3S apparatus expression and effector protein secretion (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat-1002672-g005" target="_blank">figure 5A–C</a>). The induction of T3S includes intimin expression on the outer membrane of the bacteria allowing binding to Stx-induced receptors, including nucleolin <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Robinson1" target="_blank">[32]</a>. This leads to intimate attachment and lesion formation. Secreted effector proteins can repress inflammation as can Stx <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Gobert1" target="_blank">[33]</a>–<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002672#ppat.1002672-Mhlen1" target="_blank">[39]</a>. It is proposed that the degree and nature of this modulation will be different between strains impacting on bacterial replication and therefore the extent of excretion from the animal.</p
