Honey’s Ability to Counter Bacterial Infections Arises from Both Bactericidal Compounds and QS Inhibition

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.

[1]  A. So,et al.  Critical shortage of new antibiotics in development against multidrug-resistant bacteria-Time to react is now. , 2011, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[2]  A. T. Te Velde,et al.  How honey kills bacteria , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  A. So,et al.  Tackling antibiotic resistance , 2010, BMJ : British Medical Journal.

[4]  L. Rahme,et al.  Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence , 2010, PLoS pathogens.

[5]  B. Murray,et al.  Antibiotic-resistant bugs in the 21st century--a clinical super-challenge. , 2009, The New England journal of medicine.

[6]  S. Atkinson,et al.  Quorum sensing and social networking in the microbial world , 2009, Journal of The Royal Society Interface.

[7]  T. Alandejani,et al.  Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[8]  M. Weatherall,et al.  Honey in the treatment of burns: a systematic review and meta-analysis of its efficacy. , 2009, The New Zealand medical journal.

[9]  J. Binnekade,et al.  Medical-grade honey kills antibiotic-resistant bacteria in vitro and eradicates skin colonization. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  E. Greenberg,et al.  Influence of Quorum Sensing and Iron on Twitching Motility and Biofilm Formation in Pseudomonas aeruginosa , 2007, Journal of bacteriology.

[11]  G. O’Toole,et al.  Inverse Regulation of Biofilm Formation and Swarming Motility by Pseudomonas aeruginosa PA14 , 2007, Journal of bacteriology.

[12]  Yehuda Carmeli,et al.  Multidrug-Resistant Pseudomonas aeruginosa: Risk Factors and Clinical Impact , 2006, Antimicrobial Agents and Chemotherapy.

[13]  E. Shiner,et al.  Inter-kingdom signaling: deciphering the language of acyl homoserine lactones. , 2005, FEMS microbiology reviews.

[14]  E. Pesci,et al.  Regulation of Pseudomonas Quinolone Signal Synthesis in Pseudomonas aeruginosa , 2005, Journal of bacteriology.

[15]  Eric Déziel,et al.  The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing‐regulated genes are modulated without affecting lasRI, rhlRI or the production of N‐acyl‐ l‐homoserine lactones , 2004, Molecular microbiology.

[16]  R. Tompkins,et al.  Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Hentzer,et al.  Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. , 2003, The Journal of clinical investigation.

[18]  L. Rahme,et al.  A stable isotope dilution assay for the quantification of the Pseudomonas quinolone signal in Pseudomonas aeruginosa cultures. , 2003, Biochimica et biophysica acta.

[19]  Marina S. Kuznetsova,et al.  Functions Required for Extracellular Quinolone Signaling by Pseudomonas aeruginosa , 2002, Journal of bacteriology.

[20]  L. Rahme,et al.  A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  B. Bassler.  How bacteria talk to each other: regulation of gene expression by quorum sensing. , 1999, Current opinion in microbiology.

[22]  P. Molan.  The role of honey in the management of wounds. , 1999, Journal of wound care.

[23]  F. Ausubel,et al.  Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Ausubel,et al.  Common virulence factors for bacterial pathogenicity in plants and animals. , 1995, Science.

[25]  A. Tomasz,et al.  Multiple-antibiotic-resistant pathogenic bacteria. A report on the Rockefeller University Workshop. , 1994, The New England journal of medicine.

[26]  P. Molan,et al.  A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey. , 1992, Journal of Applied Bacteriology.

[27]  S. Efem,et al.  The antimicrobial spectrum of honey and its clinical significance , 1992, Infection.

[28]  Alimuddin Zumla,et al.  Honey - A Remedy Rediscovered , 1989, Journal of the Royal Society of Medicine.

[29]  S E Efem,et al.  Clinical observations on the wound healing properties of honey , 1988, The British journal of surgery.

[30]  A. Klibanov,et al.  The mechanisms of irreversible enzyme inactivation at 100C. , 1985, Science.

[31]  B. Iglewski,et al.  A More Sensitive Plate Assay for Detection of Protease Production by Pseudomonas aeruginosa , 1979, Journal of clinical microbiology.

[32]  E. Crane.  Honey. A comprehensive survey , 1978, Medical History.

[33]  Mark T. Waters,et al.  This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Thislicensedoesnot permit commercial exploitation or the creation of derivative works without sp , 2009 .

[34]  P. Cornelis.  Pseudomonas : genomics and molecular biology , 2008 .

[35]  T. Tolker-Nielsen,et al.  Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa. , 2007, Microbiology.

[36]  El-Mashad,et al.  Antimicrobial effect of bee honey in comparison to antibiotics on organisms isolated from infected burns. , 2007, Annals of burns and fire disasters.

[37]  E. Greenberg,et al.  Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. , 2001, Annual review of genetics.

[38]  C. Echazarreta,et al.  Medical uses of honey , 1996 .

[39]  P. Molan.  The antibacterial activity of honey: 2. Variation in the potency of the antibacterial activity , 1992 .