- The hpSahul strain of Helicobacter pylori is a distinct phylogenetic population of this gram-negative, spiral-shaped bacterium, identified through multi-locus sequence typing (MLST).
- It is primarily found in Indigenous populations of Australia and New Guinea, regions historically part of the ancient Sahul landmass that connected Australia, New Guinea, and Tasmania during the Pleistocene.
- The hpSahul population is significant for its genetic isolation and its reflection of H. pylori’s co-evolution with human populations that migrated to the Sahul region approximately 50,000–60,000 years ago.
- This strain’s limited geographic distribution and deep divergence from other populations, such as hpEastAsia, hpEurope, or hpAfrica1, make it a critical subject for studying the bacterium’s evolutionary history, human migration patterns, and its role in gastric diseases among Indigenous communities with unique genetic and environmental contexts.
- Genetically, hpSahul is characterized by unique allele combinations that form a distinct clade in phylogenetic analyses, underscoring its divergence from other H. pylori populations. This divergence is attributed to the long-term isolation of Indigenous Australian and New Guinean populations, which limited genetic exchange with other human groups. Many hpSahul strains possess the cag pathogenicity island (cagPAI), encoding 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 hpSahul often features EPIYA motifs that are distinct from both Western (ABC-type) and East Asian (ABD-type) patterns, reflecting a unique evolutionary trajectory. The vacA gene typically presents as the s1m1 allele, associated with high toxicity and severe pathology, though less toxic alleles like s1m2 or s2m2 may occur in some isolates. The dupA gene, linked to duodenal ulcer risk, is variably present, with limited data on its prevalence in hpSahul. The strain’s genetic diversity, shaped by adaptation to Indigenous hosts and minimal recombination with external populations, makes it a valuable model for genomic studies.
- In terms of pathogenicity, hpSahul is associated with gastric diseases such as gastritis and peptic ulcers in Indigenous Australian and New Guinean populations, though data on gastric cancer is sparse due to underdiagnosis and limited healthcare access in these communities. The prevalence of H. pylori infection in Indigenous groups often exceeds 60–80%, driven by factors like poor sanitation and crowded living conditions. However, gastric cancer rates appear lower than in East Asia (hpEastAsia), possibly due to host genetic factors, dietary patterns, or immune modulation by co-infections, akin to the “African enigma.” The cagA-positive and vacA s1m1 genotypes in hpSahul contribute to significant inflammatory responses, but the unique EPIYA motifs may result in less oncogenic potential compared to hpEastAsia’s ABD-type. Environmental factors, such as traditional diets high in antioxidants or exposure to endemic pathogens, may further influence disease outcomes, though research on hpSahul’s clinical impact remains limited compared to other populations.
- Antibiotic resistance in hpSahul strains is poorly documented due to limited surveillance in remote Indigenous communities, but available data suggest challenges similar to those in other high-prevalence regions. In Australia, H. pylori isolates, including hpSahul, show moderate to high resistance to metronidazole (30–60%), driven by RdxA mutations, and clarithromycin resistance (10–20%), linked to A2143G mutations, is rising. Amoxicillin resistance is generally low (<5%), but fluoroquinolone and tetracycline resistance (5–15%) is emerging. These patterns complicate treatment, particularly in remote areas with limited access to antimicrobial susceptibility testing. Bismuth quadruple therapy is often recommended, but logistical barriers, including access to bismuth-based regimens, hinder effective management. The resistance profile of hpSahul highlights the need for targeted studies and culturally appropriate healthcare interventions to address H. pylori infections in Indigenous populations.
- In research, hpSahul is pivotal for elucidating H. pylori’s evolutionary dynamics and its association with ancient human migrations. Its genetic isolation provides a window into the bacterium’s adaptation to early human populations that colonized Sahul, supporting theories of a single migration wave from Asia. Comparative genomic studies with hpEastAsia, hpAsia2, and hpEurope reveal hpSahul’s unique virulence factors, such as its distinct cagA EPIYA motifs, which help explain variations in disease outcomes. The strain’s high prevalence in Indigenous communities, coupled with underreported gastric cancer rates, makes it a focus for investigating host-pathogen interactions and the impact of social determinants of health, such as access to care and environmental exposures. hpSahul’s evolutionary and clinical significance positions it as a vital strain for advancing H. pylori research, particularly in understanding the health disparities faced by Indigenous populations and informing tailored public health strategies.
