H. pylori polymorphisms affect the nature of the interaction with humans. In each panel, the H. pylori population is represented by the upper box, and the host mucosa (with epithelium and reactive neutrophils, monocytes, plasma cells, and lymphocytes) by the lower box. (a) All H. pylori cells are identical. Three polymorphic loci are shown. The lateral loci each are subject to phase variation, and each one may either be ON, encoding a full-length protein, or OFF, i.e., translation has been prematurely terminated. The middle locus represents a site in which two major alleles (represented as black and red) are present. Recombination events can permit the total or partial replacement of one locus by the other. In a, all H. pylori cells exert the same effect on the host since they are identical. (b) A single H. pylori population is present, but now individual cells are polymorphic with respect to the lateral loci. This H. pylori population will develop a different equilibrium with the host than does the population represented in a, because of its altered expression from the lateral loci. The altered host response in turn creates a different environment that selects for phenotypes different from those for a. The individual cells are thus in equilibrium with one another, and the relative proportion of one to another will be selected by the host signals. In the absence of exogenous perturbation, this model can move toward a stable equilibrium, but independent changes in the environment or periodic changes (selection) affecting the bacterial population may then move the equilibrium into new territory. (c) Two H. pylori populations are present that are recombining with one another. The dynamic equilibrium between host and the microbial population parallels that for b, except that the recombinational events change the overall equilibrium. With recombination, the variety of potential interactions expands greatly and allows a highly fluid response to host conditions. This polymorphic population can optimize overall fitness to the particular host, while remaining subject to the host selective pressures as transmitted by its signals in response to the bacterial signals. This model permits ongoing fine-adjustment of adaptation in multiple local niches.