Genetic populations and virulence factors of Helicobacter pylori

Abstract

Helicobacter pylori is a bacterium that has infected more than half of the human population worldwide. This bacterium is closely associated with serious human diseases, such as gastric cancer, and identifying and understanding factors that predict bacterial virulence is a priority. In addition, this pathogen shows high genetic diversity and co-evolution with human hosts. H. pylori population genetics, therefore, has emerged as a tool to track human demographic history. As the number of genome sequences available is increasing, studies on the evolution and virulence of H. pylori are gaining momentum. This review article summarizes the most recent findings on H. pylori virulence factors and population genetics.

Keywords: Genetic population; Helicobacter pylori; Virulence factor.

Figure 1. Overall structure of the cag PAI (A) and CagA protein (B) in H. pylori strain P12

A. Structure of the cag PAI region (~37 kb). The region comprises 28 genes that encode components of the cag-T4SS, including the CagA protein effector. B. Structure of the CagA protein (1,214 amino acid residues). The N-terminal part of CagA harbors a putative β-integrin-binding region. The C-terminal region comprises the EPIYA region, which contains EPIYA ABCC motifs and three MKI/CM/CRPIA motifs, regions that bind to the secretion chaperone CagF and contain the C-terminal secretion signal.

Figure 2. Current allelic diversity inferred from the VacA sequence

The VacA structure comprises five regions of sequence diversity referred to as the signal (s), intermediate (i) middle (m), deletion (d), and c (c) regions. The vacuolating activity of VacA varies with different alleles. In vitro, vacA s1/m1/i1 alleles show higher levels of vacuole formation than s2/m2/i2. The functions of novel polymorphic regions c and d, as well as the i3 subtype, have not yet been studied.