- The hpAsia2 strain of Helicobacter pylori is a distinct phylogenetic population of this gram-negative, spiral-shaped bacterium, identified through multi-locus sequence typing (MLST).
- Predominantly found in Central and South Asia, including regions like India, Bangladesh, and parts of Southeast Asia, hpAsia2 is a significant population due to its association with diverse human populations and its role in the evolutionary history of H. pylori. This strain reflects the bacterium’s co-evolution with human hosts, likely originating from ancient migrations across Asia, and is considered an ancestral contributor to the hybrid hpEurope population through admixture events.
- Its genetic and clinical characteristics make hpAsia2 a key strain for studying H. pylori’s adaptation to South Asian populations and its contribution to gastric diseases in regions with high infection prevalence.
- Genetically, hpAsia2 is characterized by unique allele combinations that distinguish it from other H. pylori populations, such as hpEastAsia, hpEurope, or hpAfrica1, forming a separate clade in phylogenetic analyses. Many hpAsia2 strains possess the cag pathogenicity island (cagPAI), which encodes the cagA gene and a type IV secretion system (T4SS) that injects CagA into host gastric epithelial cells, promoting inflammation and increasing the risk of peptic ulcers and gastric cancer. The cagA gene in hpAsia2 often features Western-type EPIYA motifs (ABC-type), similar to hpEurope, which are less oncogenic than the East Asian ABD-type found in hpEastAsia. The vacA gene typically presents as the s1m1 allele, associated with high toxicity and severe pathology, though s1m2 and s2m2 alleles are also present in less virulent strains. The dupA gene, linked to duodenal ulcer risk, is variably present in hpAsia2, with some isolates showing functional forms, contributing to its pathogenicity. The genetic diversity of hpAsia2, driven by recombination and adaptation to diverse South Asian populations, makes it a valuable strain for genomic and evolutionary studies.
- In terms of pathogenicity, hpAsia2 strains are associated with a range of gastric diseases, including gastritis, peptic ulcers, and gastric cancer, though the incidence of severe outcomes varies across South Asia. In countries like India and Bangladesh, where H. pylori prevalence exceeds 60–80%, hpAsia2 strains are a major cause of peptic ulcer disease, particularly duodenal ulcers, due to the presence of cagA-positive and vacA s1m1 genotypes. However, gastric cancer rates in South Asia are lower than in East Asia (hpEastAsia) but higher than in Africa (hpAfrica1), reflecting a complex interplay of bacterial virulence, host genetics, and environmental factors like spicy diets and poor sanitation. The Western-type cagA EPIYA motifs in hpAsia2 are less carcinogenic than East Asian types, which may partly explain the lower gastric cancer burden. Host factors, such as genetic polymorphisms in inflammatory genes (e.g., IL-1β), enhance disease severity in South Asian populations, though immune modulation by co-infections like helminths may mitigate progression to cancer, similar to the “African enigma.”
- Antibiotic resistance in hpAsia2 strains is a significant challenge in South Asia, where high antibiotic use drives resistance. Clarithromycin resistance, often linked to A2143G mutations, ranges from 20–40% in countries like India, making standard triple therapies (clarithromycin, amoxicillin, proton pump inhibitor) less effective. Metronidazole resistance is particularly high (50–80%), reflecting widespread use of this antibiotic, while amoxicillin resistance remains low (<10%) but is increasing. Fluoroquinolone resistance, driven by gyrA mutations, affects 15–25% of isolates, and tetracycline resistance is emerging. In response, bismuth quadruple therapy or sequential regimens are increasingly recommended in South Asia, though access to antimicrobial susceptibility testing is limited, complicating treatment. The resistance profile of hpAsia2 underscores the need for region-specific guidelines and improved diagnostic infrastructure to manage H. pylori infections effectively.
- In research, hpAsia2 is crucial for understanding H. pylori’s evolutionary dynamics and its role in human migration. Its genetic similarity to ancestral lineages that contributed to hpEurope suggests hpAsia2’s involvement in ancient population movements from Asia to Europe. Comparative genomic studies with hpEastAsia, hpEurope, and African populations highlight hpAsia2’s unique virulence factors, such as its cagA and vacA profiles, which help explain regional differences in disease outcomes. The strain’s high prevalence in South Asia, coupled with moderate gastric cancer rates, makes it a focus for investigating host-pathogen interactions and environmental influences on disease progression. hpAsia2 is also studied for its role in the spread of antibiotic resistance, particularly in densely populated regions with variable healthcare access. Its evolutionary and clinical significance positions hpAsia2 as a vital strain for advancing H. pylori research, informing public health strategies, and developing targeted therapies in South Asia.
