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Whole-Genome-Based Helicobacter pylori Geographic Surveillance: A Visualized and Expandable Webtool.

ABSTRACT: Helicobacter pylori exhibit specific geographic distributions that are related to clinical outcomes. Despite the high infection rate of H. pylori throughout the world, the genetic epidemiology surveillance of H. pylori still needs to be improved. This study used the single nucleotide polymorphisms (SNPs) profiling approach based on whole genome sequencing (WGS) to facilitate genomic population analyses of H. pylori and encourage the dissemination of microbial genotyping strategies worldwide. A total number of 1,211 public H. pylori genomes were downloaded and used to construct the typing tool, named HpTT (H. pylori Typing Tool). Combined with the metadata, we developed two levels of genomic typing, including a continent-scale and a country scale that nested in the continent scale. Results showed that Asia was the largest isolate source in our dataset, while isolates from Europe and Oceania were comparatively more widespread. More specifically, Switzerland and Australia are the main sources of widespread isolates in their corresponding continents. To integrate all the typing information and enable researchers to compare their dataset against the existing global database easily and rapidly, a user-friendly website (https://db.cngb.org/HPTT/) was developed with both genomic typing tools and visualization tools. To further confirm the validity of the website, ten newly assembled genomes were downloaded and tested precisely located on the branch as we expected. In summary, the H. pylori typing tool (HpTT) is a novel genomic epidemiological tool that can achieve high-resolution analysis of genomic typing and visualizing simultaneously, providing insights into the genetic population structure, evolution analysis, and epidemiological surveillance of H. pylori.

SUBMITTER: Jiang X

PROVIDER: S-EPMC8366602 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe emergence of multidrug-resistant Helicobacter pylori has undermined eradication strategies to prevent the development of gastric cancer. This study was conducted to estimate the prevalence of secondary antibiotic resistance of H. pylori in urban multicultural areas in Malaysia.MethodsFrom January 2017 to December 2021, gastric biopsies from 218 patients with a history of H. pylori eradication failure were sent to our laboratory for antibiotic susceptibility testing. A minimal inhibitory concentration was determined for six antibiotics, namely metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline, and rifampicin using the E-test method. Two multidrug-resistant H. pylori strains identified in this study were subjected to whole genome sequencing.ResultsEradication failure was observed to be significantly higher in the Malaysian Chinese patients than in the Malaysian Indian and Malay patients. H. pylori were successfully isolated from 51 patients (23.4%). Overall, the antibiotic resistance rates of H. pylori to metronidazole, clarithromycin, levofloxacin, and amoxicillin were 82.4% (42/51), 72.5% (37/51), 52.9% (27/51), and 3.9% (2/51), respectively. Resistance to tetracycline and rifampicin were not observed during the study period. Resistance to more than one antibiotic was observed in 82.4% (42/51) of the isolates, of which 42.2% (19/42) were resistant to three antibiotic classes. Resistance to both clarithromycin and metronidazole were most frequently observed in isolates with dual resistance (56.5%; 13/23). Codon substitutions in penicillin-binding protein 1A (V346L, V374L, G595_V596InsG, Y604H, and N608S) were detected in amoxicillin-resistance H. pylori strains. Herein, we report amoxicillin resistance in H. pylori isolated from Malaysian patients, and its resistance mechanism, for the first time.ConclusionOur results show the increase trend in secondary multidrug resistance in H. pylori isolates, which warrants continuous surveillance.

Project description:Helicobacter pylori, a Gram-negative bacterium, is associated with a wide range of gastric diseases such as gastritis, duodenal ulcer, and gastric cancer. The prevalence of H pylori and risk of disease vary in different parts of the world based on the prevailing bacterial lineage. Here, we present a contextual and comparative genomics analysis of 20 clinical isolates of H pylori from patients in Bangladesh. Despite a uniform host ethnicity (Bengali), isolates were classified as being part of the HpAsia2 (50%) or HpEurope (50%) population. Out of twenty isolates, eighteen isolates were cagA positive, with two HpEurope isolates being cagA negative, three EPIYA motif patterns (AB, AB-C, and ABC-C) were observed among the cagA-positive isolates. Three vacA genotypes were observed with the s1m1i1dic1 genotype observed in 75% of isolates; the s1m2i1d1c2 and s2m2i2d2c2 genotypes were found to be 15% and 10% of isolates, respectively. The non-virulent genotypes s2m2i2d2c2 was only observed in HpEurope population isolates. Genotypic analysis of oipA gene, present in all isolates, revealed five different patterns of the CT repeat; all HpAsia2 isolates were in "ON" while 20% of HpEurope isolates were genotypically "OFF." The three blood group antigen binding adhesins encoded genes (bab genes) examined and we observed that the most common genotype was (babA/babB/-) found in eight isolates, notably six were HpAsia2 isolates. The babA gene was found in all HpAsia2 isolates but present in only half of the HpEurope isolates. In silico antibiotic susceptibility analysis revealed that 40% of the strains were multi-drug resistant. Mutations associated with resistance to metronidazole, fluoroquinolone, and clarithromycin were detected 90%, 45%, and 5%, respectively, in H pylori strain. In conclusion, it is evident that two populations of H pylori with similar antibiotic profiles are predominant in Bangladesh, and it appears that genotypically the HpAisa2 isolates are potentially more virulent than the HpEurope isolates.

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Whole-Genome-Based Helicobacter pylori Geographic Surveillance: A Visualized and Expandable Webtool.

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