Helicobacter pylori Biofilm Formation and Its Potential Role in Pathogenesis

Abstract

Despite decades of effort, Helicobacter pylori infections remain difficult to treat. Over half of the world's population is infected by H. pylori, which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection, H. pylori localizes within the gastric mucosal layer, including deep within invaginations called glands; thanks to its impressive ability to survive despite the harsh acidic environment, it can persist for the host's lifetime. This ability to survive and persist in the stomach is associated with urease production, chemotactic motility, and the ability to adapt to the fluctuating environment. Additionally, biofilm formation has recently been suggested to play a role in colonization. Biofilms are surface-associated communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances. Biofilms pose a substantial health risk and are key contributors to many chronic and recurrent infections. This link between biofilm-associated bacteria and chronic infections likely results from an increased tolerance to conventional antibiotic treatments as well as immune system action. The role of this biofilm mode in antimicrobial treatment failure and H. pylori survival has yet to be determined. Furthermore, relatively little is known about the H. pylori biofilm structure or the genes associated with this mode of growth. In this review, therefore, we aim to highlight recent findings concerning H. pylori biofilms and the molecular mechanism of their formation. Additionally, we discuss the potential roles of biofilms in the failure of antibiotic treatment and in infection recurrence.

Keywords: Helicobacter pylori; antibiotics; biofilm; gastritis; regulation.

FIG 1

Confocal laser scanning microscopy image of an H. pylori G27 biofilm stained with the FilmTracer Live/Dead biofilm viability kit. The biofilm was formed in 96-well plates after 3 days of growth using brucella broth medium supplemented with 10% FBS. (A) Live cells; (B) dead or compromised cells; (C) merge.

FIG 2

Gastric gland colonization by H. pylori. H. pylori SS1 was visualized by green fluorescent protein (GFP) expression (green), while gland cells were stained by using DNA Hoechst fluorescent dye (blue).

FIG 3

Schematic representation of an H. pylori biofilm. Extracellular polymeric substances in H. pylori, composed of extracellular DNA, extracellular proteins, and OMVs, may act as a shield to protect the bacterial community from immune cells and antimicrobials.