Phenolic Compounds from Humulus lupulus as Natural Antimicrobial Products: New Weapons in the Fight against Methicillin Resistant Staphylococcus aureus, Leishmania mexicana and Trypanosoma brucei Strains

Abstract

New anti-infective agents are urgently needed to fight microbial resistance. Methicillin-resistant Staphylococcus aureus (MRSA) strains are particularly responsible for complicated pathologies that are difficult to treat due to their virulence and the formation of persistent biofilms forming a complex protecting shell. Parasitic infections caused by Trypanosoma brucei and Leishmania mexicana are also of global concern, because of the mortality due to the low number of safe and effective treatments. Female inflorescences of hop produce specialized metabolites known for their antimicrobial effects but underexploited to fight against drug-resistant microorganisms. In this study, we assessed the antimicrobial potential of phenolic compounds against MRSA clinical isolates, T. brucei and L. mexicana. By fractionation process, we purified the major prenylated chalcones and acylphloroglucinols, which were quantified by UHPLC-UV in different plant parts, showing their higher content in the active flowers extract. Their potent antibacterial action (MIC < 1 µg/mL for the most active compound) was demonstrated against MRSA strains, through kill curves, post-antibiotic effects, anti-biofilm assays and synergy studies with antibiotics. An antiparasitic activity was also shown for some purified compounds, particularly on T. brucei (IC50 < 1 to 11 µg/mL). Their cytotoxic activity was assessed both on cancer and non-cancer human cell lines.

Hop Extract: An Efficacious Antimicrobial and Anti-biofilm Agent Against Multidrug-Resistant Staphylococci Strains and Cutibacterium acnes

“…In particular, the increase in MRSA and vancomycin-resistant S. aureus strains is a challenge in the actual clinical practice ( Oliveira et al, 2018 ). MRSA are microorganisms responsible for most skin and hospital-acquired infections, associated with a high level of mortality ( Bocquet et al, 2019 ). The methicillin resistance is due to the acquisition of gene encoding for a penicillin-binding protein 2a (PBP2a), reducing the β-lactam action ( Peacock and Paterson, 2015 ).…”

Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G

“…5- O -Methylglovanon, a prenylated flavanone isolated from Glycosmis plants, inhibited the growth of ampicillin resistant S. aureus and Staphylococcus epidermidis isolates with MICs ranging from 12.5 to 50 µg/mL and showed synergy with ampicillin against same isolates ( Zhou et al, 2011 ). Xanthohumol, a prenylated chalcone in hop ( Humulus lupulus L.), was found to synergize with several antibiotics (ciprofloxacin, gentamicin, oxacillin, rifampicin) against MRSA isolate while its desmethyl derivative was synergistic only with ciprofloxacin and gentamicin ( Bocquet et al, 2019 ).…”

MeJA Elicitation of Chicory Hairy Roots Promotes Efficient Increase of 3,5-diCQA Accumulation, a Potent Antioxidant and Antibacterial Molecule

“…The extract, sub-extracts or pure compounds dissolved in MeOH or MeOH/water were incorporated into Mueller-Hinton Agar (MHA) (Oxoid Agar, Thermofisher Scientific, Waltham, Mass., USA) at final concentrations ranging from 0.078 to 1.25 mg.mL −1 . The final proportion of methanol in the medium did not exceed 5%, a concentration that did not affect the bacterial growth [ 60 ]. A multi-headed inoculator allowed spotting bacterial strains at 10 5 CFU.mL −1 in cysteinated Ringer solution (Merck ® , Darmstadt, Germany).…”