Antimicrobial Evaluation of Various Honey Types against Carbapenemase-Producing Gram-Negative Clinical Isolates

Abstract

The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as an agent to treat several infections and wound injuries. Nevertheless, the antibacterial effect of honey was mostly evaluated against Gram-positive bacteria. Hence, the objective of our study was to evaluate the antibacterial activity, as well as the physicochemical parameters, of genuine Greek honeys against multidrug-resistant Gram-negative pathogenic bacteria. In this vein, we aimed to study the in vitro antibacterial potential of rare Greek honeys against Verona integron-encoded metallo-β-lactamase (VIM)- or Klebsiella pneumoniae carbapenemase-producing multidrug-resistant Gram-negative pathogens. Physicochemical parameters such as pH, hydrogen peroxide, free acidity, lactonic acid, total phenols total flavonoids, free radical scavenging activities, tyrosinase enzyme inhibitory activity and kojic acid were examined. Moreover, the antimicrobial activity of 10 different honey types was evaluated in five consecutive dilutions (75%, 50%, 25%, 12.5% and 6.25%) against the clinical isolates by the well diffusion method, as well as by the determination of the minimum inhibition concentration after the addition of catalase and protease. Almost all the physicochemical parameters varied significantly among the different honeys. Fir and manuka honey showed the highest values in pH and H2O2, while the free acidity and lactonic acid levels were higher in chestnut honey. Total phenols, total flavonoids and free radical scavenging activities were found higher in cotton, arbutus and manuka honey, and finally, manuka and oregano honeys showed higher tyrosinase inhibition activity and kojic acid levels. The antimicrobial susceptibility depended on the type of honey, on its dilution, on the treatment methodology and on the microorganism. Arbutus honey was the most potent against VIM-producing Enterobacter cloacae subsp. dissolvens in 75% concentration, while fir honey was more lethal for the same microorganism in the 25% concentration. Many honeys outperformed manuka honey in their antibacterial potency. It is of interest that, for any given concentration in the well diffusion method and for any given type of honey, significant differences were not detected among the four multidrug-resistant pathogens, which explains that the damaging effect to the bacterial cells was the same regardless of the bacterial species or strain. Although the antimicrobial potency of different honey varieties dependents on their geographical origin and on their compositional differences, the exact underlying mechanism remains yet unclear.

Anti-Inflammatory and Antibacterial Effects and Mode of Action of Greek Arbutus, Chestnut, and Fir Honey in Mouse Models of Inflammation and Sepsis

“…A plethora of in vitro studies on anti-inflammatory properties of honey flavonoids suggest that these compounds are important modulators of inflammatory processes. In vitro evaluation of the total phenolic and flavonoid content as well as the free radical scavenging activities of arbutus, fir, and chestnut honeys revealed potent antioxidant and anti-inflammatory properties [26]. Flavonoids exert their anti-inflammatory action via two mechanisms [9].…”

“…Previous evidence showed that Greek honey types derived from different botanical origins and geographical locations displayed antibacterial properties in vitro against Gramnegative multidrug-resistant bacteria, such as Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa [26]. The aim of this study was to further evaluate the in vivo anti-inflammatory and antibacterial potential of these honey varieties, namely, arbutus honey, chestnut honey, and two fir honey samples, while Manuka honey served as the control, using mouse models of acute inflammation and polymicrobial peritonitis.…”

Sequence-Specific Electrochemical Genosensor for Rapid Detection of blaOXA-51-like Gene in Acinetobacter baumannii

“…The emergence of antibiotic-resistant bacteria causing infection in humans is a major global concern [ 48 ]. A. baumannii is one of the important pathogens that is included in this antibiotic-resistant bacteria group and is responsible for many hospital-acquired infections [ 6 , 9 ].…”

Interactions between Medical Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination Effects

“…Therefore, the use of modern methods, antimicrobial testing with standardized protocols, and quality controls of plant materials are necessary. For example, studying mechanisms using molecular biology methods for the identified plant-derived bioactive compounds individually in combination may possibly facilitate the development of more efficient new antimicrobial agents [ 165 ]. Further studies on the complete analysis of the molecular interaction profiles of the bioactive compounds are needed to provide a more detailed picture of their antimicrobial activity.…”

“…Studies on untargeted methods to identify molecular targets of synergy and unknown synergistic or antagonistic mechanisms of action will be of great importance. Integrated methods completing tasks such as the identification of bioactive mixture compounds [ 165 ], the determination of the nature of their interactions, and the classification of their mechanisms of action simultaneously should be developed. Moreover, biomarkers derived from bioactive compounds that regulate synergistic interactions may be essential for defining treatment strategies.…”