Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Abstract

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

Biological investigation of N-methyl thiosemicarbazones as antimicrobial agents and bacterial carbonic anhydrases inhibitors

“…Also in bacterial and fungal kingdoms, CAs play crucial roles in the growth, pathogenicity, and virulence, and structural differences of the four microbial CAs classes (α, β, γ, and ι) with respect to α-isoforms in humans (hCA I and hCA II) were observed, laying the foundation for the development of highly selective inhibitors 17–23 . Notably, relevant proof-of-concept between the CA inhibition and the in vivo antibacterial efficacy confirmed this valuable strategy 24–27 and several CAs from S. aureus, E. coli , P. aeruginosa, H. pylori, and other microorganisms were recently detected and characterised, allowing the design of nanomolar inhibitors 16 , 20 , 28–34 .…”

GC/MS analysis and potential synergistic effect of mandarin and marjoram oils on Helicobacter pylori

“…The continuous evolution of many drawbacks with the current therapies for H. pylori, such as the prevalence of antibiotic-resistant, drug interventions, side effects, and poor satisfaction, all highlight the search for safe and effective non-antibiotic alternative medicines 5 . This has driven our interest in evaluating the bactericidal activity of marjoram and mandarin oils against H. pylori.…”

“…Standard medications can cure the infection in more than 80% of H. pylori -infected patients. Patient compliance, antibiotic resistance, and recurring infections, on the other hand, are all the major concerns that limit the use of antibiotics in the treatment of H. pylori infection that needs to be addressed 4 , 5 .…”

In Vitro Activity of the Arylaminoartemisinin GC012 against Helicobacter pylori and Its Effects on Biofilm

“…The samples were rinsed with PBS and then air dried for 30 min. The dye associated with the biofilms was dissolved with 1 mL of 33% acetic acid, and 200 μL was used to measure the absorbance at 590 nm [ 60 ] with a microplate reader (Synergy IV, Biotek Instruments, Winooski, VT, USA) to determine the amount of biofilm formation.…”