DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.Helicobacter pylori is a microaerophilic bacterium with the extraordinary ability to establish infections in human stomachs that can last for years or decades, despite immune and inflammatory responses and normal turnover of the gastric epithelium and overlying mucin layer in which it resides. It is carried by more than half of all people worldwide and has attracted great attention as a major cause of peptic ulcer disease and an early risk factor for gastric cancer, one of the most frequently lethal of malignancies worldwide (for reviews see references 23, 48, and 60).

During the time of egg deposition, schistosome-infected mice exhibit a downregulation in interleukin 2 and interferon y production toward parasite antigens, mitogens, and foreign nonparasite protein antigens. To determine whether this imbalance in cytokine response would impact on CD8+ cytotoxic T-lymphocyte (CTL) responses, as well as on immune clearance of viral infections, we challenged Schistosoma mansoni-infected BALB/c mice, when cytokine imbalance was prominent, with a recombinant vaccinia virus expressing human immunodeficiency virus type 1 gpl60. In contrast to control vaccinia-infected animals, S. mansoni plus vaccinia-infected mice did not produce significant Thl cytokine responses upon in vitro stimulation with recombinant gpl20, consistent with previous results for nonparasite antigens. However, more striking was the downregulation ofthe virus-specific CTL response not previously studied. Spleen cells from vaccinia-infected control mice displayed strong CD8+ cytolytic activity against gpl60-transfected fibroblasts and fibroblasts pulsed with a peptide (P18) representing a CTL epitope of gpl60. In contrast, mice coinfected with S. mansoni and vaccinia manifested absent or markedly reduced in vitro CTL activity even in the presence of exogenous interleukin 2. To determine whether this immune dysregulation might impact on viral clearance, we measured virus titers in tissues as a function of time. Mice infected with vaccinia virus alone rapidly cleared the virus, whereas in animals coinfected with S. mansoni, viral clearance was delayed by as much as 3 weeks in the liver and by several days in the spleen and lungs. These observations suggest that helminth infection may influence immune responses to concurrent viral infections.Schistosomiasis is a major human parasitic infection with an estimated prevalence of >200 million people (1). In certain parts of the world, schistosomiasis is frequently associated with hepatitis B infection (2, 3), although the nature of the relationship is unclear. Schistosomiasis, in common with other helminth infections, is characterized by eosinophilia, elevated IgE levels (4), and mastocytosis. These responses are known to be controlled by cytokines produced primarily by CD4+ lymphocytes belonging to the Th2 subset (5). Recent evidence from murine experimental models indicates that concomitant with an increase in Th2 cytokine production, helminth infections also cause a downregulation of cytokines [interleukin 2 (IL-2) and interferon y (IFN-'y)] characteristic of the Thl subset of CD4+ cells (6, 7). In the case of patent schistosome infections (i.e., after the onset of egg laying), this increase in Th2 cytokines (IL-4, IL-5, and IL-10) and reduction in Thl cytokines extends to stimulation by mitogens and injected foreign protein as well as schistosome antigens (6,8,9 MATERIALS AND METHODS Parasite and Viral Infections and Determination of ViralTiters in Tissues. Ten-to 12-week-old female BALB/c mice (National Cancer Institute, Frederick, MD) were infected percutaneo...

Summary The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori‐positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet‐associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori‐positive and three H. pylori‐negative) patients recognized H. pylori cytotoxin‐associated gene A (CagA) protein, and in three completely responsive patients, levels of anti‐CagA antibody in platelet eluates declined after eradication therapy. Cross‐reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.

Acetobacter species have been used for brewing traditional vinegar and are known to have genetic instability. To clarify the mutability, Acetobacter pasteurianus NBRC 3283, which forms a multi-phenotype cell complex, was subjected to genome DNA sequencing. The genome analysis revealed that there are more than 280 transposons and five genes with hyper-mutable tandem repeats as common features in the genome consisting of a 2.9-Mb chromosome and six plasmids. There were three single nucleotide mutations and five transposon insertions in 32 isolates from the cell complex. The A. pasteurianus hyper-mutability was applied for breeding a temperature-resistant strain grown at an unviable high-temperature (42°C). The genomic DNA sequence of a heritable mutant showing temperature resistance was analyzed by mutation mapping, illustrating that a 92-kb deletion and three single nucleotide mutations occurred in the genome during the adaptation. Alpha-proteobacteria including A. pasteurianus consists of many intracellular symbionts and parasites, and their genomes show increased evolution rates and intensive genome reduction. However, A. pasteurianus is assumed to be a free-living bacterium, it may have the potentiality to evolve to fit in natural niches of seasonal fruits and flowers with other organisms, such as yeasts and lactic acid bacteria.