Helicobacter pylori Biofilm Formation and Its Potential Role in Pathogenesis

Abstract

Despite decades of effort, infections remain difficult to treat. Over half of the world's population is infected by, which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection, 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 survival has yet to be determined. Furthermore, relatively little is known about the biofilm structure or the genes associated with this mode of growth. In this review, therefore, we aim to highlight recent findings concerning 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.

The Helicobacter pylori biofilm involves a multi-gene stress-biased response including a structural role for flagella

“…Biofilms contained mainly coccoid cells along with some rod-shaped cells (Fig. 7A), as described previously for H. pylori biofilms (20-23). When compared to planktonic populations, the proportion of both morphologies were similar at ∼ 80% coccoid cells (data not shown).…”

“…Chronicity and recalcitrant infections are also common features associated with H. pylori (19). Yet, the role of biofilm growth in promoting H. pylori persistence is still not clear (20). The first suggestion of biofilm formation by H. pylori during colonization of the human gastric mucosa was found using biopsies and scanning electron microscopy (SEM) analysis (20-22).…”

“…Yet, the role of biofilm growth in promoting H. pylori persistence is still not clear (20). The first suggestion of biofilm formation by H. pylori during colonization of the human gastric mucosa was found using biopsies and scanning electron microscopy (SEM) analysis (20-22). These studies demonstrated that gastric biopsy samples from H. pylori -positive patients showed dense layers of bacteria aggregated and attached to the mucosal surface.…”

“…The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were increased by 16-and 4-fold, respectively, in the biofilm cells as compared to planktonic ones (26). However, despite the growing evidences of H. pylori biofilm formation both in vitro and in vivo (20-22,24), little is known about the genes involved in biofilm formation. We thus sought to characterize H. pylori biofilm and investigate global transcriptional changes during biofilm formation, with a particular focus on H. pylori strain SS1 because it is able to colonize mice and thus will be able to serve as a model for biofilm formation in vivo .…”

Helicobacter pylori biofilm cells are metabolically distinct, express flagella, and antibiotic tolerant

“…Although the molecular mechanisms that drive H. pylori biofilm formation are not fully elucidated, several factors associated with H. pylori biofilm have been identified using high throughput strategies such as genomics, transcriptomics, and proteomics (Shao, Sun et al 2013, Wong, Ng et al 2016, Hathroubi, Servetas et al 2018, Hathroubi, Zerebinski et al 2018. Genes expressed to high levels in the biofilm include several genes or products of the cytotoxinassociated gene pathogenicity island (cagPAI) which encode for a type IV secretion system, the cagPAI substrate CagA, as well as diverse membrane proteins (Shao, Sun et al 2013, Wong, Ng et al 2016.…”