Abstract
The clinical associations and correlations with other virulence factors such as cag pathogenicity island (PAI) of the Integrating Conjugative Elements Helicobacter pylori TFSS (ICEHptfs), a new type IV secretion system (TFSS) in H. pylori has not been described. Among 103 studied strains from Indonesia, almost all strains (99.0%) contained cag PAI with more than half (55.8%) were intact cag PAI. Patients infected with intact cag PAI strains showed significantly higher antral activity, inflammation and atrophy as well as corporal inflammation than those with non-intact cag PAI strains, confirming the virulence of cag PAI. Over half of strains (53.8%) contained ICEHptfs, predominantly consisted of ICEHptfs3-tfs4a (42.8%) and ICEHptfs3 (16.3%). Although patients infected with ICEHptfs-positive strains had lower H. pylori density, those with the complete ICEHptfs4b strains tended to have higher antral activity than the negative one. In combination, patients infected with combination of intact cag PAI-ICEHptfs-positive strains had more severe inflammation than those with non-intact cag PAI-ICEHptfs-negative, suggesting a possibility of a mutual correlation between these TFSS(s).
Highlights
Helicobacter pylori is a human-specific bacterium, colonizing the stomach of approximately 50% of the modern human population[1]
With the increasing number of H. pylori complete genomes deposited in the GenBank, plasticity regions are considered as conserved mobile elements, rather than a region with genomic plasticity, and are usually organized as a complete set of TFSS machinery
We performed endoscopic examination on 1072 dyspeptic patients in 17 cities in Indonesia from August 2012 to August 2016, and a total of 103 H. pylori were isolated from patients (66 male and 37 female; mean age 49.2 ± 13 years; range 24–80 years), comprising 92 patients with gastritis, 10 with peptic ulcer disease (PUD) and 1 with gastric cancer
Summary
Helicobacter pylori is a human-specific bacterium, colonizing the stomach of approximately 50% of the modern human population[1]. The TFSS4 possesses sub-type based on nucleotide diversity in the virB2, virB3, virB4, topA, virB7 and virB8, discriminating TFSS4a and TFSS4b, and diversity in virB11, virD4 and virD2, distinguishing TFSS4a and TFSS4c16 The terminology of this region was inconsistent in several previous studies. The 6 bp deletion-type is unique type among East Asian-type CagA since almost all pre-EPIYA motif types of strains isolated from Japan and Vietnam was reported to have 39 bp deletion-type and 18 bp deletion-type, respectively[22] Patients infected with this 6 bp deletion-type/East Asian-type CagA strains showed to have lower gastric mucosal histologic scores compared to those with Western-type CagA23, it is well known that East Asian-type CagA had generally more virulent than Western-type CagA. We reported the distribution of ICEHptfs in Indonesia using high throughput next-generation sequencing technology and revealed that strains from some geographic areas lack this genomic region, and the intactness of this region had an association with clinical outcome
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