Myricetin as an Antivirulence Compound Interfering with a Morphological Transformation into Coccoid Forms and Potentiating Activity of Antibiotics against Helicobacter pylori

Abstract

Helicobacter pylori, a gastric pathogen associated with a broad range of stomach diseases, has a high tendency to become resistant to antibiotics. One of the most important factors related to therapeutic failures is its ability to change from a spiral to a coccoid form. Therefore, the main aim of our original article was to determine the influence of myricetin, a natural compound with an antivirulence action, on the morphological transformation of H. pylori and check the potential of myricetin to increase the activity of antibiotics against this pathogen. We observed that sub-minimal inhibitory concentrations (sub-MICs) of this compound have the ability to slow down the process of transformation into coccoid forms and reduce biofilm formation of this bacterium. Using checkerboard assays, we noticed that the exposure of H. pylori to sub-MICs of myricetin enabled a 4–16-fold reduction in MICs of all classically used antibiotics (amoxicillin, clarithromycin, tetracycline, metronidazole, and levofloxacin). Additionally, RT-qPCR studies of genes related to the H. pylori morphogenesis showed a decrease in their expression during exposure to myricetin. This inhibitory effect was more strongly seen for genes involved in the muropeptide monomers shortening (csd3, csd6, csd4, and amiA), suggesting their significant participation in the spiral-to-coccoid transition. To our knowledge, this is the first research showing the ability of any compound to synergistically interact with all five antibiotics against H. pylori and the first one showing the capacity of a natural substance to interfere with the morphological transition of H. pylori from spiral to coccoid forms.

Antimicrobial Effect of a Proteolytic Enzyme From the Fruits of Solanum granuloso-leprosum (Dunal) Against Helicobacter pylori

“…According to recent reports, some flavonoid compounds have shown synergism when combined with anti- H. pylori first-line antibiotics ( 63 , 64 ).…”

Fighting the Antibiotic Crisis: Flavonoids as Promising Antibacterial Drugs Against Helicobacter pylori Infection

“…Myricetin strongly inhibited the expression of genes involved in the morphological transition of H. pylori from spiral to coccoid forms, thereby avoiding the increase in antimicrobial resistance associated with cell shape transformation, which has been observed in this pathogen. Consequently, myricetin induced a 4–16-fold reduction in the MIC values of CLR, MTZ, LVX, TET, and AMX ( Krzyzek et al., 2021 ). In addition, several authors suggest that the proven damage triggered by certain flavonoids in the cytoplasmic membrane and/or cell wall could enhance the susceptibility of bacterial pathogens to the action of antibiotics ( Amin et al., 2015 ; Sanhueza et al., 2017 ).…”

In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori

“…To assess the anti-biofilm activity of all 10 tested compounds against H. pylori J99, the crystal violet staining method was applied [ 96 ]. Bacteria in a final density of 10 7 CFU/mL were suspended in 1 mL of BHI broth with 5% fetal calf serum and a gradient concentration (2–256 µg/mL) of the tested compounds, and were cultured for 3 days under microaerophilic atmosphere, 37 °C, and 50 rpm shaking.…”