scholarly journals Identification of New Helicobacter pylori Subpopulations in Native Americans and Mestizos From Peru

2020 ◽  
Vol 11 ◽  
Author(s):  
Andrés Julián Gutiérrez-Escobar ◽  
Billie Velapatiño ◽  
Victor Borda ◽  
Charles S. Rabkin ◽  
Eduardo Tarazona-Santos ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Native Americans ◽  
Purifying Selection ◽  
Native Communities ◽  
Genome Wide ◽  
Genome Wide Data ◽  
H Pylori ◽  
Phylogenetic Profiling ◽  
Native Group ◽  
Andean Highlands

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

scholarly journals Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution

2021 ◽  
Vol 9 (2) ◽  
pp. 240
Author(s):  
Bruno Cavadas ◽  
Marina Leite ◽  
Nicole Pedro ◽  
Ana C. Magalhães ◽  
Joana Melo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Host Response ◽  
Homo Sapiens ◽  
European Ancestry ◽  
Genome Wide ◽  
Expression Host ◽  
H Pylori ◽  
Human Ancestry

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

scholarly journals Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates

2021 ◽  
Vol 7 (11) ◽  
Author(s):  
Vo Phuoc Tuan ◽  
Koji Yahara ◽  
Ho Dang Quy Dung ◽  
Tran Thanh Binh ◽  
Pham Huu Tung ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Type Species ◽  
Genetic Variations ◽  
Genome Wide Association ◽  
Content Type ◽  
Link Type ◽  
Genome Wide ◽  
H Pylori

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori , which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori -related diseases.

scholarly journals Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets for Helicobacter pylori-Induced Gastric Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohamed Tarek Badr ◽  
Mohamed Omar ◽  
Georg Häcker
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Cell Line ◽  
Gene Signature ◽  
Genome Wide Association ◽  
Expression Studies ◽  
Genome Wide ◽  
Human Pathology ◽  
Gene Expression Studies ◽  
H Pylori

Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa and can lead to gastric inflammation, ulcers, and stomach cancer. Due to the increase in H. pylori antimicrobial resistance new methods to identify the molecular mechanisms of H. pylori-induced pathology are urgently needed. Here we utilized a computational biology approach, harnessing genome-wide association and gene expression studies to identify genes and pathways determining disease development. We mined gene expression data related to H. pylori-infection and its complications from publicly available databases to identify four human datasets as discovery datasets and used two different multi-cohort analysis pipelines to define a H. pylori-induced gene signature. An initial Helicobacter-signature was curated using the MetaIntegrator pipeline and validated in cell line model datasets. With this approach we identified cell line models that best match gene regulation in human pathology. A second analysis pipeline through NetworkAnalyst was used to refine our initial signature. This approach defined a 55-gene signature that is stably deregulated in disease conditions. The 55-gene signature was validated in datasets from human gastric adenocarcinomas and could separate tumor from normal tissue. As only a small number of H. pylori patients develop cancer, this gene-signature must interact with other host and environmental factors to initiate tumorigenesis. We tested for possible interactions between our curated gene signature and host genomic background mutations and polymorphisms by integrating genome-wide association studies (GWAS) and known oncogenes. We analyzed public databases to identify genes harboring single nucleotide polymorphisms (SNPs) associated with gastric pathologies and driver genes in gastric cancers. Using this approach, we identified 37 genes from GWA studies and 61 oncogenes, which were used with our 55-gene signature to map gene-gene interaction networks. In conclusion, our analysis defines a unique gene signature driven by H. pylori-infection at early phases and that remains relevant through different stages of pathology up to gastric cancer, a stage where H. pylori itself is rarely detectable. Furthermore, this signature elucidates many factors of host gene and pathway regulation in infection and can be used as a target for drug repurposing and testing of infection models suitability to investigate human infection.

scholarly journals Continental-scale genomic analysis suggests shared post-admixture adaptation in Americas

2020 ◽  
Author(s):  
Linda Ongaro ◽  
Mayukh Mondal ◽  
Rodrigo Flores ◽  
Davide Marnetto ◽  
Ludovica Molinaro ◽  
...  
Keyword(s):  
Natural Selection ◽  
Native Americans ◽  
Genomic Analysis ◽  
Human Leukocyte ◽  
System Response ◽  
Continental Scale ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Human Leukocyte Antigen Locus ◽  
Genomic Regions

AbstractAmerican populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, despite the fact that gene-flow could drive adaptive evolution, it is not clear whether and how natural selection acted on the resulting genetic variation in the Americas.In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ∼6,000 admixed individuals from ten American countries. In doing so, we identified regions characterized by a Divergent Ancestry Profile (DAP), in which a significant over or under ancestral representation is evident.Our results highlighted a series of genomic regions with Divergent Ancestry Profiles (DAP) associated with immune system response and relevant medical traits, with the longest DAP region encompassing the Human Leukocyte Antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analyzing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts, and characterized by a high deleteriousness score.Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at continental scale in the Americas, affecting more often functional and impactful genomic variants.

scholarly journals Rapid evolution of the Helicobacter pylori AlpA adhesin in a high gastric cancer risk region from Colombia

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4846 ◽  
Author(s):  
Andrés Julián Gutiérrez-Escobar ◽  
Gina Méndez-Callejas ◽  
Orlando Acevedo ◽  
Maria Mercedes Bravo
Keyword(s):  
Helicobacter Pylori ◽  
Critical Role ◽  
Rapid Evolution ◽  
Purifying Selection ◽  
Clinical Isolates ◽  
Gastric Epithelial Cells ◽  
Gastric Cancer Risk ◽  
Diagnostic Strategies ◽  
Variation Patterns ◽  
H Pylori

To be able to survive, Helicobacter pylori must adhere to the gastric epithelial cells of its human host. For this purpose, the bacterium employs an array of adhesins, for example, AlpA. The adhesin AlpA has been proposed as a major adhesin because of its critical role in human stomach colonization. Therefore, understanding how AlpA evolved could be important for the development of new diagnostic strategies. However, the genetic variation and microevolutionary patterns of alpA have not been described in Colombia. The study aim was to describe the variation patterns and microevolutionary process of alpA in Colombian clinical isolates of H. pylori. The existing polymorphisms, which are deviations from the neutral model of molecular evolution, and the genetic differentiation of the alpA gene from Colombian clinical isolates of H. pylori were determined. The analysis shows that gene conversion and purifying selection have shaped the evolution of three different variants of alpA in Colombia.

scholarly journals Glycosaminoglycan biosynthesis pathway in host genome is associated with Helicobacter pylori infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dingxue Hu ◽  
Yueqi Lu ◽  
Daoming Wang ◽  
Chao Nie ◽  
Yan Li
Keyword(s):  
Helicobacter Pylori ◽  
Chinese Population ◽  
Association Studies ◽  
Host Susceptibility ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Gastric Diseases ◽  
Association Analyses ◽  
Genome Wide ◽  
H Pylori

AbstractHelicobacter pylori is a causative pathogen of many gastric and extra-gastric diseases. It has infected about half of the global population. There were no genome-wide association studies (GWAS) for H. pylori infection conducted in Chinese population, who carried different and relatively homogenous strain of H. pylori. In this work, we performed SNP (single nucleotide polymorphism)-based, gene-based and pathway-based genome-wide association analyses to investigate the genetic basis of host susceptibility to H. pylori infection in 480 Chinese individuals. We also profiled the composition and function of the gut microbiota between H. pylori infection cases and controls. We found several genes and pathways associated with H. pylori infection (P < 0.05), replicated one previously reported SNP rs10004195 in TLR1 gene region (P = 0.02). We also found that glycosaminoglycan biosynthesis related pathway was associated with both onset and progression of H. pylori infection. In the gut microbiome association study, we identified 2 species, 3 genera and several pathways had differential abundance between H. pylori infected cases and controls. This paper is the first GWAS for H. pylori infection in Chinese population, and we combined the genetic and microbial data to comprehensively discuss the basis of host susceptibility to H. pylori infection.

scholarly journals In Vivo Dissection of the Helicobacter pylori Fur Regulatory Circuit by Genome-Wide Location Analysis

2006 ◽  
Vol 188 (13) ◽  
pp. 4654-4662 ◽  
Author(s):  
Alberto Danielli ◽  
Davide Roncarati ◽  
Isabel Delany ◽  
Valentina Chiarini ◽  
Rino Rappuoli ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Pathogenic Bacteria ◽  
Iron Homeostasis ◽  
Location Analysis ◽  
Transcriptional Level ◽  
Regulatory Circuit ◽  
Genome Wide ◽  
A Genome ◽  
H Pylori

ABSTRACT Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. In Helicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type and fur deletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by the fur mutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes, hpn2 and flaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in the fur mutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level in H. pylori and points to regulatory functions extending beyond the classical Fur repression paradigm.

The rod-to-coccoid body transformation in cultures of Helicobacter pylori

1990 ◽  
Vol 48 (3) ◽  
pp. 626-627
Author(s):  
A. R. Crooker ◽  
W. G. Kraft ◽  
T. L. Beard ◽  
M. C. Myers
Keyword(s):  
Helicobacter Pylori ◽  
Growth Cycle ◽  
Negative Bacterium ◽  
Body Formation ◽  
Coccoid Form ◽  
Spiral Form ◽  
Prolonged Culture ◽  
H Pylori ◽  
Upper Gastrointestinal

Helicobacter pylori is a microaerophilic, gram-negative bacterium found in the upper gastrointestinal tract of humans. There is strong evidence that H. pylori is important in the etiology of gastritis; the bacterium may also be a major predisposing cause of peptic ulceration. On the gastric mucosa, the organism exists as a spiral form with one to seven sheathed flagella at one (usually) or both poles. Short spirals were seen in the first successful culture of the organism in 1983. In 1984, Marshall and Warren reported a coccoid form in older cultures. Since that time, other workers have observed rod and coccal forms in vitro; coccoid forms predominate in cultures 3-7 days old. We sought to examine the growth cycle of H. pylori in prolonged culture and the mode of coccoid body formation.

Peptische Ulzera und Helicobacter pylori: Wie wir wissen, was wir wissen

2015 ◽  
Vol 72 (7) ◽  
pp. 475-480
Author(s):  
Raphael Scholl
Keyword(s):  
Helicobacter Pylori ◽  
Kontrollierte Studie ◽  
H Pylori ◽  
Peptische Ulzera

Zusammenfassung. Zu den wichtigsten Ursachen peptischer Ulzera gehört das Bakterium Helicobacter pylori. Aber wie wurde dieser ursächliche Zusammenhang nachgewiesen? Aufschluss darüber gibt die Geschichte und Theorie einer Reihe einschlägiger Studien, die in den 1980er Jahren durchgeführt wurden. Am Anfang stand die Entdeckung einer blossen Korrelation zwischen dem neu entdeckten Bakterium und peptischen Ulzera in Magenbiopsien. Unklar blieb, ob das Bakterium die Krankheit verursachte, oder ob es bloss eine opportunistische bakterielle Besiedlung darstellte. Ohne Tiermodell war der experimentelle Nachweis der Richtung der Verursachung jedoch schwierig: Zwar wurde in einem couragierten Selbstversuch mit einer geschluckten Bakterienkultur eine Gastritis beobachtet – aber der Einzelfall war wenig aussagekräftig. Die Schwächen des Selbstversuchs liessen sich durch eine randomisierte, Plazebo-kontrollierte Studie beheben, die den Anforderungen des dritten Koch’schen Postulats gerecht wurde. Darüber hinaus war es notwendig, erste Aufschlüsse über den Mechanismus der ursächlichen Verbindung zwischen H. pylori und peptischen Ulzera zu gewinnen: Wie zum Beispiel kann das Bakterium im sauren Milieu des Magens überleben? Die wissenschaftshistorische und wissenschaftstheoretische Betrachtung des Falls illustriert, wie medizinisches Wissen schrittweise aufgebaut wird.

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