Comparative genomics analysis of statistically significant genomic islands of Helicobacter pylori strains for better understanding the disease prognosis.

Joyeeta Chakraborty,Raghunath Chatterjee

doi:10.1042/bsr20212084

Abstract

Bacterial virulence factors are often located in their genomic islands (GIs). Helicobacter pylori, a highly diverse organism is reported to be associated with several gastrointestinal diseases like, gastritis, gastric cancer (GC), peptic ulcer, duodenal ulcer (DU) etc. A novel similarity score (Sm)-based comparative analysis with GIs of 50 H. pylori strains revealed clear idea of the various factors which promote disease progression. Two putative pathogenic GIs in some of the H. pylori strains were identified. One GI, having a putative labile enterotoxin and other dynamin-like proteins (DLPs), is predicted to increase the release of toxin by membrane vesicular formation. Another island contains a virulence-associated protein D (vapD) which is a component of a type-II toxin–antitoxin system (TAs), leads to enhance the severity of the H. pylori infection. Besides the well-known virulence factors like Cytotoxin-associated gene A (CagA) and vacA, several GIs have been identified which showed to have direct or indirect impact on H. pylori clinical outcomes. One such GI, containing lipopolysaccharide (LPS) biosynthesis genes was revealed to be directly connected with disease development by inhibiting the immune response. Another collagenase-containing GI worsens ulcers by slowing down the healing process. GI consisted of fliD operon was found to be connected to flagellar assembly and biofilm production. By residing in biofilms, bacteria can avoid antibiotic therapy, resulting in chronic infection. Along with well-studied CagA and vacuolating toxin A (vacA) virulent genes, it is equally important to study these identified virulence factors for better understanding H. pylori-induced disease prognosis.

Highlights

Helicobacter pylori, formerly known as Campylobacter pylori, is a Gram-negative, microaerophilic bacteria that is part of the gastric microbiota in over 50% of population worldwide
H. pylori infection leads to a variety of upper gastrointestinal disorders, such as chronic gastritis, peptic ulcer disease (PUD), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer (GC) [4–6]
Characterization of the detected Genomic Island (GI) gave an idea of their impact in the H. pylori colonization, infection and disease prognosis

Summary

Introduction

Helicobacter pylori, formerly known as Campylobacter pylori, is a Gram-negative, microaerophilic bacteria that is part of the gastric microbiota in over 50% of population worldwide. Strain-specific virulence factors are generally located in the Genomic Island (GI) region of particular pathogenic strains. Large genomic regions consisting of multiple horizontally transferred genes (HTGs) are collectively termed as GIs [7]. This identified virulence factor was not present in beneficial strains of E. coli This cluster of genes was referred to as pathogenicity islands (PAIs). Studying H. pylori at strain level may shed light to understand the disease prognosis. The comparative study with the GIs among 50 H. pylori strains identified GIs with virulence-associated genes in addition to the known GIs. Further characterization of the newly detected islands identified the possible function of these GIs. Several other factors were identified which were found to be associated either directly or indirectly with the H. pylori-induced disease prognosis

Methods

Results

Discussion