Rapid Characterization of Virulence Determinants in Helicobacter pylori Isolated from Non-Atrophic Gastritis Patients by Next-Generation Sequencing

Frank Imkamp; Francis N Lauener; Daniel Pohl; Philippe Lehours; Filipa F Vale; Quentin Jehanne; Reinhard Zbinden; Peter M Keller; Karoline Wagner

doi:10.3390/jcm8071030

Rapid Characterization of Virulence Determinants in Helicobacter pylori Isolated from Non-Atrophic Gastritis Patients by Next-Generation Sequencing

J Clin Med. 2019 Jul 12;8(7):1030. doi: 10.3390/jcm8071030.

Authors

Frank Imkamp¹, Francis N Lauener¹, Daniel Pohl², Philippe Lehours^{3

4}, Filipa F Vale⁵, Quentin Jehanne⁴, Reinhard Zbinden¹, Peter M Keller¹, Karoline Wagner⁶

Affiliations

¹ Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland.
² Gastroenterology Division, University Hospital of Zurich, 8006 Zurich, Switzerland.
³ INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, 33076 Bordeaux, France.
⁴ French National Reference Centre for Campylobacter and Helicobacter, Bordeaux Hospital, 33076 Bordeaux, France.
⁵ Host-Pathogen Interactions Unit, Research Institute for Medicine (iMed-ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal.
⁶ Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland. karoline.wagner@usb.ch.

Abstract

Helicobacter pylori is a major human pathogen that causes a wide range of gastrointestinal pathology. Progression of H. pylori induced gastritis to more severe disease has been found to highly correlate with the array of virulence factors expressed by the pathogen. The objective of this study was twofold: first, to characterize the genetic diversity of H. pylori strains isolated from 41 non-atrophic gastritis patients in Switzerland, an issue that has not been investigated to date. And second, to assess the prevalence and sequence variation of H. pylori virulence factors (cagA, vacA, iceA and dupA) and genes encoding outer membrane proteins (OMPs; babA, babB, sabA, sabB, hopZ, hopQ and oipA) by whole genome sequencing (WGS) using an Illumina MiSeq platform. WGS identified high genetic diversity in the analyzed H. pylori strains. Most H. pylori isolates were assigned to hpEurope (95.0%, 39/41), and the remaining ones (5.0%, 2/41) to hpEastAsia, subpopulation hspEAsia. Analysis of virulence factors revealed that 43.9% of the strains were cagA-positive, and the vacA s1 allele was detected in 56.0% of the isolates. The presence of cagA was found to be significantly associated (P < 0.001) with the presence of vacA s1, babA2 and hopQ allele 1 as well as expression of oipA. Moreover, we found an association between the grade of gastritis and H. pylori abundance in the gastric mucosa, respectively and the presence of cagA, vacA s1 and hopQ allele 1. Among our 41 gastritis patients, we identified seven patients infected with H. pylori strains that carried a specific combination of virulence factors (i.e., cagA, vacA s1 allele and babA2 allele), recently implicated in the development of more severe gastrointestinal pathology, like peptic ulcer disease and even gastric cancer. To this end, WGS can be employed for rapid and detailed characterization of virulence determinants in H. pylori, providing valuable insights into the pathogenic capacity of the bacterium. This could ultimately lead to a higher level of personalized treatment and management of patients suffering from H. pylori associated infections.

Keywords: Helicobacter pylori; babA; babB; cagA; dupA; gastritis; hopQ; hopZ; iceA; next generation sequencing; oipA; sabA; sabB; vacA; virulence.