Honey's Ability to Counter Bacterial Infections Arises from Both Bactericidal Compounds and QS Inhibition - PubMed (original) (raw)
Honey's Ability to Counter Bacterial Infections Arises from Both Bactericidal Compounds and QS Inhibition
Rui Wang et al. Front Microbiol. 2012.
Abstract
The ability of honey to kill bacterial pathogens in vitro and quickly clear even chronic or drug-resistant infections has been demonstrated by several studies. Most current research is focused on identifying the bactericidal compounds in honey, but the action of the compounds discovered is not sufficient to explain honey's activity. By diluting honey to sub-inhibitory levels, we were able to study its impact on bacterial coordinated behavior, and discovered that honey inhibits bacterial quorum sensing (QS). Experiments to characterize and quantify honey's effect on the QS networks of Pseudomonas aeruginosa revealed that low concentrations of honey inhibited the expression of MvfR, las, and rhl regulons, including the associated virulence factors. This research also establishes that inhibition of QS is associated with honey's sugar content. Therefore, honey combats infections by two independent mechanisms acting in tandem: bactericidal components, which actively kill cells, and disruption of QS, which weakens bacterial coordination and virulence.
Keywords: Pseudomonas; QS inhibition; anti-infective; honey; infection; mvfR(pqsR); quorum-sensing; sugars.
Figures
Figure 1
Honey inhibits expression of QS-related genes and molecules. (A) Shows manuka honey (MH) contains heat-sensitive bactericidal compounds. Raw MH, heat-treated MH and distilled water were dropped onto a P. aeruginosa lawn. Strains used were PA14 and a pqsA mutant. (B) Indicates honey contains a compound that reduces expression of pqsA. PA14 was grown in solutions of 2, 4, and 6% MH and pqsA expression was measured using a GFP (ASV) gene as a reporter. Fluorescence indicates pqsA expression, plotted here as a function of time. (C) Indicates inhibition of pqsA gene expression by honey is independent of honey source and unaffected by heat treatment. Experiment was performed as in (A), with all honeys diluted to 4%. Samples used were MH and local honey (LH), with and without heat treatment. (D) The expression of lasI and rhlI genes in the presence of honey was measured using a Miller β-galactosidase assay with PA14 cells expressing lasI or rhlI driven by the lacZ promoter and a lasR<lasI double mutant cells as a negative control. Measurements were taken at OD600 nm = 1.0 and 2.0 to determine gene expression at different cell densities. (E,F) Shows concentrations of MvfR low molecular weight QS-regulated molecules produced by the pqsABCD operon in the presence of honey. Samples used were MH and LH, with and without heat treatment.
Figure 2
Honey impacts production of virulence factors. (A) Indicates honey decreases the production of pyocyanin, a virulence factor regulated by the MvfR QS network of P. aeruginosa. Pyocyanin is displayed as a percentage normalized to the control (no honey added). (B) demonstrates the effect on extracellular protease production by honey. Milk plates were inoculated with 2 μL of bacterial culture and incubated for 48 h at 24°C.
Figure 3
The effects of honey on QS-related genes and virulence factors can be reproduced by comparable sugar solutions. (A) Indicates that the inhibitory effect of diluted honey on pqsA can be reproduced using sugar solutions. (B) Shows the effect on extracellular proteases caused by 2.5% glucose in milk plates.
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