Identification of strain-specific genes located outside the plasticity zone in nine clinical isolates of Helicobacter pylori
            
               
                  b
               
            
            
               
                  bThe GenBank accession numbers for the H. pylori sequences reported in this paper are AF326599–AF326607 for region A, AF326608–AF326616 for region B, AF326617–AF326625 for region C, AF326626–AF326634 for region D, AF327212–AF327220 for region E, AF328909–AF3289

Chanto, Grettel; Occhialini, Alessandra; Gras, Nathalie; Alm, Richard A.; Mégraud, Françis; Marais, Armelle

doi:10.1099/00221287-148-11-3671

Cited by 22 publications

(10 citation statements)

References 41 publications

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“…The ORFs coding for HcpA, HcpC, and HcpE are conserved in the genome sequences of strains 26695 and J99, whereas HP0336, the ORF coding for HcpB, is absent from the genome of strain J99. HP0336 was also found to be absent from the genomes of nine clinical isolates, as shown by Chanto and coworkers (4). In five of nine cases, HP0336 was replaced by JHP0318.…”

Section: Discussionmentioning

confidence: 73%

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Detection of High Titers of Antibody against Helicobacter Cysteine-Rich Proteins A, B, C, and E in Helicobacter pylori -Infected Individuals

Mittl

Lüthy

Reinhardt

et al. 2003

Clin Vaccine Immunol

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Section: Discussionmentioning

confidence: 73%

“…The loci for HP0336 and JHP0318 were investigated in nine H. pylori strains that were isolated from individuals who suffered from gastric carcinoma, duodenal ulcers, and chronic gastritis. HP0336 was found to be absent from all strains, whereas JHP0318 was detected in five strains (4).…”

mentioning

confidence: 98%

Detection of High Titers of Antibody against Helicobacter Cysteine-Rich Proteins A, B, C, and E in Helicobacter pylori -Infected Individuals

Mittl

Lüthy

Reinhardt

et al. 2003

Clin Vaccine Immunol

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“…Interestingly, one previously documented case of a recombination event between two strain populations in a single infected individual defined at the sequence level involved the cag PAI, a highly variable genomic region (30). The locus where we observed a recombination event also has a highly mosaic structure in the sequenced strains, as well as a number of clinical isolates (12). Thus, targeting such regions in addition to the housekeeping and virulence genes commonly used in MLST studies should help workers characterize the generation of diversity in H. pylori strains.…”

Section: Discussionmentioning

confidence: 79%

Genetic Analysis of Helicobacter pylori Strain Populations Colonizing the Stomach at Different Times Postinfection

et al. 2007

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Genetic diversity of the human gastric pathogen Helicobacter pylori in an individual host has been observed; whether this diversity represents diversification of a founding strain or a mixed infection with distinct strain populations is not clear. To examine this issue, we analyzed multiple single-colony isolates from two to four separate stomach biopsies of eight adult and four pediatric patients from a high-incidence Mexican population. Eleven of the 12 patients contained isolates with identical random amplified polymorphic DNA, amplified fragment length polymorphism, and vacA allele molecular footprints, whereas a single adult patient had two distinct profiles. Comparative genomic hybridization using whole-genome microarrays (array CGH) revealed variation in 24 to 67 genes in isolates from patients with similar molecular footprints. The one patient with distinct profiles contained two strain populations differing at 113 gene loci, including the cag pathogenicity island virulence genes. The two strain populations in this single host had different spatial distributions in the stomach and exhibited very limited genetic exchange. The total genetic divergence and pairwise genetic divergence between isolates from adults and isolates from children were not statistically different. We also analyzed isolates obtained 15 and 90 days after experimental infection of humans and found no evidence of genetic divergence, indicating that transmission to a new host does not induce rapid genetic changes in the bacterial population in the human stomach. Our data suggest that humans are infected with a population of closely related strains that vary at a small number of gene loci, that this population of strains may already be present when an infection is acquired, and that even during superinfection genetic exchange among distinct strains is rare.

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“…However, these individual domains undergo extensive duplications and rearrangements to make up to 50 distinct domain combinations. This extensive mosaicism (99, 100) suggests that these proteins are rapidly evolving because of a dynamic conflict either with the Helicobacter host or with other competing parasitic elements.…”

Section: Resultsmentioning

confidence: 99%

Polyvalent Proteins, a Pervasive Theme in the Intergenomic Biological Conflicts of Bacteriophages and Conjugative Elements

et al. 2017

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Intense biological conflicts between prokaryotic genomes and their genomic parasites have resulted in an arms race in terms of the molecular “weaponry” deployed on both sides. Using a recursive computational approach, we uncovered a remarkable class of multidomain proteins with 2 to 15 domains in the same polypeptide deployed by viruses and plasmids in such conflicts. Domain architectures and genomic contexts indicate that they are part of a widespread conflict strategy involving proteins injected into the host cell along with parasite DNA during the earliest phase of infection. Their unique feature is the combination of domains with highly disparate biochemical activities in the same polypeptide; accordingly, we term them polyvalent proteins. Of the 131 domains in polyvalent proteins, a large fraction are enzymatic domains predicted to modify proteins, target nucleic acids, alter nucleotide signaling/metabolism, and attack peptidoglycan or cytoskeletal components. They further contain nucleic acid-binding domains, virion structural domains, and 40 novel uncharacterized domains. Analysis of their architectural network reveals both pervasive common themes and specialized strategies for conjugative elements and plasmids or (pro)phages. The themes include likely processing of multidomain polypeptides by zincin-like metallopeptidases and mechanisms to counter restriction or CRISPR/Cas systems and jump-start transcription or replication. DNA-binding domains acquired by eukaryotes from such systems have been reused in XPC/RAD4-dependent DNA repair and mitochondrial genome replication in kinetoplastids. Characterization of the novel domains discovered here, such as RNases and peptidases, are likely to aid in the development of new reagents and elucidation of the spread of antibiotic resistance.IMPORTANCE This is the first report of the widespread presence of large proteins, termed polyvalent proteins, predicted to be transmitted by genomic parasites such as conjugative elements, plasmids, and phages during the initial phase of infection along with their DNA. They are typified by the presence of multiple domains with disparate activities combined in the same protein. While some of these domains are predicted to assist the invasive element in replication, transcription, or protection of their DNA, several are likely to target various host defense systems or modify the host to favor the parasite's life cycle. Notably, DNA-binding domains from these systems have been transferred to eukaryotes, where they have been incorporated into DNA repair and mitochondrial genome replication systems.

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Cited by 22 publications

References 41 publications

Detection of High Titers of Antibody against Helicobacter Cysteine-Rich Proteins A, B, C, and E in Helicobacter pylori -Infected Individuals

Detection of High Titers of Antibody against Helicobacter Cysteine-Rich Proteins A, B, C, and E in Helicobacter pylori -Infected Individuals

Genetic Analysis of Helicobacter pylori Strain Populations Colonizing the Stomach at Different Times Postinfection

Polyvalent Proteins, a Pervasive Theme in the Intergenomic Biological Conflicts of Bacteriophages and Conjugative Elements

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