Nonfimbrial Adhesin Mutants Reveal Divergent Escherichia coli O157:H7 Adherence Mechanisms on Human and Cattle Epithelial Cells

Figure 8

Proposed models driving SS-RSE adherence phenotypes. Based on our data from the EDL933 mutants and the SS17 SNP data, we propose the following models that begin to explain the unique adherence phenotype exhibited by SS isolates on RSE cells. At present, we do not have enough data to narrow down the list of mechanisms, but we propose three possible mechanisms that may be involved in these phenomena. (a) change in interactions with membrane-bound transcriptional regulators (MBTR) such as quorum regulators or σ-factors for example. Many global regulators reside in the membranes of Escherichia coli and they most likely interact with outer membrane proteins and adhesins. The left panel describes the genetic state of EDL933 adhering to RSE cells where an outer membrane protein (for example, YfaL) can interact with a MBTR. However, in the right panel displaying SS17 with RSE cells, mutations in that transporter (or as is the example with OmpA, mutations with the MBTR) disrupt this regular connection allowing for downstream upregulation of target genes including those involved in adherence to RSE cells and aggregation of the O157:H7 cells. (b) Epigenetic changes can also occur due to changes in the genetic code. In this example, the panel to the left shows the EDL933 mutants and SS17’s proposed genome landscape with hypothetical sites of epigenetic regulation. In the case of the right, top panel, in EDL933 parent strain, the epigenetic activity is distributed to express the transporters shown. However, other adhesins and aggregation protein genes may not have preference due to sequence affinity for those enzymes. When SS17 acquired SNPs in these genes or the gene is deleted (as is the case with EDL933ΔompA), the preference switches to lower affinity sites, thus upregulating these other adhesins and aggregation genes. (c) The final model we propose is one that changes the function of neighboring proteins or protein partners of these genes and their gene products. In this example, an autotransporter can interact with another adhesin/aggregation protein in the membrane. This gives the two adhesins a specific yet separate function as they act together. This change in interaction, however, may drive a change in general function and thus a change in phenotype, in this example from a diffuse but strong adherence to a more aggregative and stronger adherence. This change could cause another adhesin or both adhesins to coordinately become stronger and thus drive higher adherence and aggregation, just as it would if these genes were deleted (as in the EDL933 mutants). One alternative to this same hypothesis is a change in another adhesin that we have not tested that interacts with one of the receptors that was tested but does not exhibit an nsSNP (such as OmpA). If the other receptor change caused the dissociation in SS17, a deletion of ompA (in this example) would cause the same dissociation in EDL933, causing the change in EDL933’s adherence phenotype.

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