Sains Malaysiana 53(3)(2024): 605-621

http://doi.org/10.17576/jsm-2024-5303-10

Functional Analysis of cag Pathogenicity Island Diversity in Helicobacter pylori Isolated from Multi-Ethnic Patients in Malaysia

(Analisis Fungsian Kepelbagaian Pulau Kepatogenan cag dalam Helicobacter pylori Dipencilkan daripada Pesakit Pelbagai Etnik di Malaysia)

SHAZA AZLIN RAZAK¹, ALFIZAH HANAFIAH^1,*, ASIF SUKRI², HUI-MIN NEOH³ &

 NORAZIAH MOHAMAD ZIN⁴

¹Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia

²Department of Biological Sciences and Biotechnology, Faculty of Science and Technology,

Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

³UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia

⁴Programme of Biomedical Science, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia

Diserahkan: 13 Oktober 2023/Diterima: 9 Februari2024

Abstract

cagPAI is an important pathogenic marker contributing to disease severity caused by H. pylori infection, encoding proteins for type four secretion systems (T4SS) and the pro-inflammatory cytokines (IL-8) induction in infected host. The heterogeneity of cagPAI genes results in different clinical outcomes in H. pylori infection. The aim of this study was to investigate the functional diversity of cagPAI genes in clinical H. pylori strains isolated from patients with gastroduodenal diseases. Among the isolates investigated, 6 out of 27 (22.2%) harbor intact cagPAI, 3 strains (11.1%) have complete absence of cagPAI, and 18 strains (66.7%) contain a partially deleted island. IL-8 concentration is observed significantly higher among cagPAI-positive isolates (P = 0.045). Of note, IL-8 secretion in the gastric cells infected with H. pylori strains isolated from Malay patients was significantly higher than the gastric cells infected with the strains from non-Malay patients (P = 0.046). The secretion of IL-8 appears in similarly high among intact and partially deleted cagPAI isolates. East Asian cagA isolates induce a notably higher level of IL-8 than that of Western cagA. Inflammatory activities are observed and IL-8 concentration in the milder stage was found in significantly higher quantities than in the severe stage (P = 0.027). The ‘hummingbird’ phenotype was observed to cause severe effects in infected cells with cagPAI-intact H. pylori. The genetic variability of cagPAI isolates from multi-ethnicity patients may have unique implications for disease outcomes with respect to proinflammatory secretion.

Keywords: CagA; cagPAI; Helicobacter pylori; ‘hummingbird’ phenotype; interleukin-8

Abstrak

cagPAI merupakan penanda patogen yang penting dalam mempengaruhi keterukan penyakit akibat jangkitan Helicobacter pylori, yang mana ia mengekod sistem perembesan jenis empat (T4SS) serta rembesan pro-radang sitokin (IL-8) dalam hos.  Perbezaan dalam hasil klinikal kerana jangkitan H. pylori adalah akibat daripada kepelbagaian gen cagPAI.  Tujuan penyelidikan ini adalah untuk mengkaji variasi kefungsian gen cagPAI bagi strain klinikal H. pylori daripada pesakit gastrousus.  Keutuhan cagPAI yang lengkap dikesan terhadap 6 daripada 27 strain (22%) kajian, manakala 3 strain (11.1%) tidak mempunyai cagPAI dan 18 strain (66.7%) mengandungi cagPAI separa lengkap. Kepekatan IL-8 adalah lebih tinggi setelah dijangkiti pencilan positif-cagPAI (P = 0.045). Tambahan lagi rembesan IL-8 akibat jangkitan isolat H. pylori daripada pesakit Melayu adalah secara signifikannya lebih tinggi berbanding infeksi terhadap sel gastrik dalam kalangan pesakit bukan Melayu (P = 0.046). Rembesan IL-8 pencilan yang utuh cagPAI dengan cagPAI tidak lengkap adalah pada aras yang tinggi. Kepekatan IL-8 akibat jangkitan isolat cagA Timur Asia dilihat lebih tinggi berbanding isolat cagA Barat.  Pemerhatian terhadap aktiviti keradangan mendapati kepekatan IL-8 pada peringkat yang lebih ringan adalah nyata sekali lebih banyak berbanding peringkat yang teruk (P = 0.027). Jangkitan H. pylori yang utuh cagPAI dilihat menyebabkan fenotip ‘hummingbird’ yang lebih teruk terhadap sel. Kepelbagaian genetik isolat cagPAI daripada pesakit berbilang etnik berkemungkinan memberi implikasi unik berkenaan dengan rembesan proinflamasi terhadap hasil penyakit.

Kata kunci: CagA; cagPAI; fenotip ‘hummingbird’; Helicobacter pylori; interleukin-8

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*Pengarang untuk surat-menyurat; email: alfizah@ppukm.ukm.edu.my