Helicobacter pylori Efflux Pumps: A Double-Edged Sword in Antibiotic Resistance and Biofilm Formation

Abstract

Helicobacter pylori is a major pathogen associated with various gastric diseases. Despite decades of research, the treatment of H. pylori remains challenging. One of the primary mechanisms contributing to failures of therapies targeting this bacterium is genetic mutations in drug target sites, although the growing body of scientific data highlights that efflux pumps may also take part in this process. Efflux pumps are proteinaceous transporters actively expelling antimicrobial agents from the interior of the targeted cells and reducing the intracellular concentration of these compounds. Considering that efflux pumps contribute to both antimicrobial resistance and biofilm formation, an in-depth understanding of their properties may constitute a cornerstone in the development of novel therapeutics against H. pylori. In line with this, the aim of the current review is to describe the multitude of efflux pumps produced by H. pylori and present the data describing the involvement of these proteins in tolerance and/or resistance to various classes of antimicrobial substances.

Keywords: Helicobacter pylori; antibiotic resistance; antibiotic tolerance; biofilm; efflux pumps; efflux systems; transporters.

Figure 1

A diagrammatic representation of four superfamilies of efflux pumps present in Helicobacter pylori. Representatives of each superfamily are provided below the scheme.

Figure 2

A schematic drawing showing a response of H. pylori to the antimicrobial exposure. This adaptative response is associated with changes in the expression profile of genes encoding efflux pumps and metabolic transporters during the planktonic-to-biofilm transition of Helicobacter pylori, which as a result lead to tolerance and/or multidrug resistance against antimicrobials.