Culture-free Helicobacter pylori genomics reveals within-host virulence heterogeneity and antibiotic resistance
Year: 2026
Type: preprint
Abstract: Helicobacter pylori (Hp) infects over 40% of the world population and causes most cases of gastric cancer worldwide, yet fundamental questions about its within-host genetic diversity remain unresolved. Decades of work on Hp genomics depends on culturing clinical isolates, which can distort within-host genetic heterogeneity that informs Hp virulence and antimicrobial resistance. Culture-free alternatives have been limited by the extremely low Hp abundance in gastric tissue (usually 10^-3 to 10^-7 of total genomic DNA), making direct metagenomics prohibitively expensive and existing enrichment strategies insufficient for whole-genome recovery. Here we develop ultra-sensitive Hp sequencing (uHp-seq) for reconstructing Hp genomes directly from gastric biopsies. uHp-seq achieves a thousand-fold Hp DNA enrichment and recovers near-complete genomes across samples spanning orders of magnitude in Hp abundance. Notably, individual hosts may harbor multiple co-existing Hp strains or cagA EPIYA variants with different oncogenic potential. Resistance-associated variants for six commonly used antibiotics are resolved with greater accuracy than PCR-based and probe-based commercial panels. Applied to minimally invasive gastric string samples, uHp-seq delivers reliable resistance profiles without endoscopy, opening a path to genome-guided Hp eradication.
Source: medRxiv
Authors: Yujie Liu, Mi Ni, Xue-Song Zhang, Jessica Bass, Panchajanya Deshpande, Judith Romero-Gallo, Hao Chen, Yu Fan, Difei Wang, Wanjin Qiao, Yanchun Zhang, Edward A. Mead, Emmanuel Dias-Neto, Alejandro Corvalan, Rachel Brody, Constanza M. Camargo, Wendy Szymczak, Amy D. Klion, Richard M. Peek, Martin J. Blaser, Gang Fang
Institutions: Icahn School of Medicine at Mount Sinai, Rutgers, The State University of New Jersey, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Albert Einstein College of Medicine, Montefiore Medical Center, Vanderbilt University, Vanderbilt University Medical Center, Division of Cancer Epidemiology and Genetics, Rutgers Cancer Institute, Pontificia Universidad Católica de Chile
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223674215