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    Beyond Low Prevalence: Exploring Antibiotic Resistance and Virulence Profiles in Sri Lankan <i>Helicobacter pylori</i> with Comparative Genomics
    (MDPI AG, 2025-01-16)
    Fauzia, Kartika Afrida
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    Rathnayake, Jeewantha
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    Doohan, Dalla
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    Lamawansa, Meegahalande Durage
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    Alfaray, Ricky Indra
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    Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh
    (MDPI AG, 2023-01-31)
    Fauzia, Kartika Afrida
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    Aftab, Hafeza
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    Tshibangu-Kabamba, Evariste
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    Alfaray, Ricky Indra
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    Beyond Low Prevalence: Exploring Antibiotic Resistance and Virulence Profiles in Sri Lankan Helicobacter pylori with Comparative Genomics
    (MDPI AG, 2025-02-14)
    Fauzia, Kartika Afrida
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    Rathnayake, Jeewantha
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    Doohan, Dalla
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    Lamawansa, Meegahalande Durage
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    Alfaray, Ricky Indra
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    Utilization of an Automated Latex Agglutination Turbidity Assay for Assessing Gastric Mucosal Alteration during Helicobacter pylori Infection
    (The Editorial Office of Gut and Liver, 2024-01)
    Khangai, Ayush
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    Akada, Junko
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    ; ;
    Azzaya, Dashdorj
    BACKGROUND/AIMS: : A latex agglutination turbidity (LA) assay to test for serum antibodies has been approved in Japan and Korea for mass screening of Helicobacter pylori infection. In this study, we evaluated the LA assay for diagnosing H. pylori infection and predicting gastric mucosal changes in a Mongolian population. METHODS: : In total, 484 individuals were classified into H. pylori-positive (n=356) and H. pylori-negative (n=128) groups, as determined by histology and H. pylori culture. RESULTS: : The best cutoff, sensitivity, and specificity values for the LA assay were 18.35 U/mL, 74.2%, and 65.6%, respectively. The LA values in the atrophic gastritis group were statistically higher than those in the other groups (healthy, chronic gastritis, intestinal metaplasia, and gastric cancer, p<0.0001). The cutoff value to distinguish the atrophic gastritis group from the other four groups was 32.0 U/mL, and its area under the curve was 0.673, which was the highest among the E-plate, pepsinogen (PG) I, PG II, and PG I/II ratio tests in our data. The odds ratios for atrophic gastritis determined by the LA assay and PG I test in multiple logistic regression were 2.5 and 1.9, respectively, which were significantly higher than for the other tests. CONCLUSIONS: : The LA assay can determine the risk of atrophic gastritis, which in turn is a considerable risk factor for gastric cancer. We propose using this assay in combination with the PG I/II ratio to avoid missing gastric cancer patients who have a low LA value (less than 32.0 U/mL).
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    Fine-scale population structure of Japanese Helicobacter pylori provides new anthropological and epidemiological insights
    (2025-06)
    Tomonari, Kohei
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    Alfaray, Ricky Indra
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    Fauzia, Kartika Afrida
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    Matsunari, Osamu
    Helicobacter pylori is considered to contribute to gastric cancer and is also used as a marker to trace human migration due to its co-evolution with humans. To understand the recently proposed tripartite model suggesting three ancestral origins for the Japanese population and address the enigma of the high incidence of gastric cancer in Northeast Hondo (Hondo is mainland Japan), we conducted a fine-scale population structure analysis using a large Japanese H. pylori dataset, including 438 strains from 9 regions based on whole-genome sequences. As a result of fineSTRUCTURE analysis, it was found that H. pylori in Northeast Hondo is genetically distinct from hspEAsia subgroup 7 (sg7), which is widely distributed elsewhere in Hondo. We named this new subgroup hspEAsia-sg8 (Northeast Hondo). Ancestry analysis using ChromoPainter revealed that, while a large proportion of the genomes of hspEAsia-sg8 strains were painted by donors from their own population, the ancestry components of hspEAsia-sg7 showed a high proportion of Chinese and Korean components, suggesting that they were formed through admixture with continental hspEAsia subgroups. These results align with human genome studies, which indicate an original ancestry component in Northeast Hondo and a higher proportion of East Asian components in West Hondo, supporting the tripartite model. This also suggests novel potential for biogeographic ancestry inference in forensic science, as the H. pylori genome can distinguish Hondo populations. Furthermore, fixation index analysis comparing the genome of hspEAsia-sg8 with other Japanese hspEAsia subgroups revealed a high number of nonsynonymous mutations in hp0378 (ccsBA) and hp0377 (dsbC/ccmG). Because these genes are involved in cytochrome c maturation and disulphide bond formation, the detected mutations may affect bacterial survival, growth or pathogenicity. This study supports the tripartite model for the formation of modern Japanese people and suggests that the strain of H. pylori prevalent in the Northeast Hondo region may contribute to the high incidence of gastric cancer there.
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    Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study
    (MDPI AG, 2023-09) ;
    Alfaray, Ricky Indra
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    Oyuntsetseg, Khasag
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    Khangai, Ayush
    BACKGROUND: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, most Helicobacter pylori strains in Mongolia have a less virulent Western-type CagA. We aimed to determine how H. pylori genomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. METHODS: We identified a set of 274 virulence-associated genes in H. pylori, including virulence factor and outer membrane protein (OMP) genes, the type four secretion system gene cluster, and 13 well-known virulence gene genotypes in 223 H. pylori strains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158 H. pylori strains (15 gastric cancer and 143 non-gastric cancer strains). RESULTS: Out of 274 genes, we found 13 genes were variable depending on disease outcome, especially iron regulating OMP genes. H. pylori strains from Mongolia were divided into two main subgroups: subgroup (Sg1) with high risk and Sg2 with low risk for gastric cancer. The general characteristics of Sg1 strains are that they possess more virulence genotype genes. We found nine non-synonymous single nucleotide polymorphisms in seven genes that are linked with gastric cancer strains. CONCLUSIONS: Highly virulent H. pylori strains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.
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    Exploring Alternative Treatment Choices for Multidrug-Resistant Clinical Strains of Helicobacter pylori in Mongolia
    (MDPI AG, 2023-11)
    Khangai, Ayush
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    Azzaya, Dashdorj
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    Oyuntsetseg, Khasag
    Helicobacter pylori is a pathogen related to severe diseases such as gastric cancer; because of rising antimicrobial-resistant strains, failure to eradicate H. pylori with antibiotics has increased worldwide. Multidrug-resistant H. pylori and gastric cancer is common in Mongolia; therefore, we aimed to explore alternative antimicrobial treatments and the genomes of resistant strains in this country. A total of 361 H. pylori strains isolated from patients in Mongolia were considered. Minimal inhibitory concentrations for two fluoroquinolones (ciprofloxacin and moxifloxacin), rifabutin, and furazolidone were determined via two-fold agar dilution. Genomic mutations in antibiotic-resistant strains were identified by next-generation sequencing using the Illumina Miseq platform and compared with genes from a reference H. pylori strain (26695). The resistance rate of H. pylori strains to quinolones was high (44% to ciprofloxacin and 42% to moxifloxacin), and resistance to rifabutin was low (0.5%); none were resistant to furazolidone. Most quinolone-resistant strains possessed gyrA gene mutations causing amino acid changes (e.g., N87K, A88P, and D91G/Y/N). While one rifabutin-resistant strain had amino acid-substituting mutations in rpoB (D530N and R701C), the other had three novel rpoB mutations; both rifabutin-resistant strains were sensitive to furazolidone. Overall, our findings suggest that rifabutin and/or furazolidone may be an alternative, effective H. pylori treatment in patients who have failed to respond to other treatment regimens.