Transformation of Helicobacter pylori into Coccoid Forms as a Challenge for Research Determining Activity of Antimicrobial Substances

Abstract

Morphological variability is one of the phenotypic features related to adaptation of microorganisms to stressful environmental conditions and increased tolerance to antimicrobial substances. Helicobacter pylori, a gastric mucosal pathogen, is characterized by a high heterogeneity and an ability to transform from a spiral to a coccoid form. The presence of the coccoid form is associated with the capacity to avoid immune system detection and to promote therapeutic failures. For this reason, it seems that the investigation for new, alternative methods combating H. pylori should include research of coccoid forms of this pathogen. The current review aimed at collecting information about the activity of antibacterial substances against H. pylori in the context of the morphological variability of this bacterium. The collected data was discussed in terms of the type of substances used, applied research techniques, and interpretation of results. The review was extended by a polemic on the limitations in determining the viability of coccoid H. pylori forms. Finally, recommendations which can help in future research aiming to find new compounds with a potential to eradicate H. pylori have been formulated.

Keywords: H. pylori; antibacterial therapies; coccoid forms; morphological transformation.

Figure 1

Diagram presenting the activity of classically used antibiotics and proton pump inhibitors (PPIs) against Helicobacter pylori.

Figure 2

Diagram presenting activity of plant extracts and plant-derived compounds against Helicobacter pylori.

Figure 3

Diagram presenting activity of synthetic compounds against Helicobacter pylori.

Figure 4

Diagram presenting activity of fatty acids and their derivatives against Helicobacter pylori.

Figure 5

Diagram presenting activity of peptides against Helicobacter pylori.

Figure 6

Physiological and morphological changes of coccoid H. pylori forms contributing to difficulties in the proper interpretation of viability during the antibacterial activity determination. Symbols: extracellular DNA (eDNA), outer membrane vesicles (OMVs).

Figure 7

Representative photos of H. pylori cells taken with transmission electron microscopy (TEM). (A) Mixed population of spiral/rod-shaped and coccoid cells. (B) Population of coccoid cells in different physiological states. (C) Coccoid cell after degradation (cell lysis). Symbols: coccoid form with dense cytosol (white arrow), coccoid form with “empty cytosol” (empty arrow), irregularly- shaped coccoid form (white arrowhead), outer membrane vesicles (white stars). Scale bar is equal to 0.2 µm.