antibacterial effects of manuka honey: mechanistic insights

Abstract: Antimicrobial resistance (AMR) is an increasing clinical problem precipitated by the
inappropriate use of antibiotics in the later parts of the 20th Century. This problem, coupled with
the lack of novel therapeutics
in the development pipeline, means AMR is reaching crisis point,
with an expected annual death rate of ten million people worldwide by 2050. To reduce, and
to potentially remedy this problem, many researchers are looking into natural compounds with
antimicrobial and/or antivirulence activity. Manuka honey is an ancient antimicrobial remedy
with a good track record against a wide range of nosocomial pathogens that have increased AMR.
Its inhibitory effects are the result of its constituent components, which add varying degrees
of antimicrobial efficacy to the overall activity of manuka honey. The antimicrobial efficacy of
manuka honey and some of its constituent components (such as methylglyoxal and leptosperin)
are known to bestow some degree of antimicrobial efficacy to manuka honey. Despite growing
in vitro evidence of its antimicrobial efficacy, the in vivo use of manuka honey (especially in a
clinical environment) has been unexpectedly slow, partly due to the lack of mechanistic data. The
mechanism by which manuka honey achieves its inhibitory efficacy has recently been identified
against Staphylococcus aureus and Pseudomonas aeruginosa, with both of these contrasting
organisms being inhibited through different mechanisms. Manuka honey inhibits S. aureus by
interfering with the cell division process, whereas P. aeruginosa cells lyse in its presence due to
the reduction of a key structural protein. In addition to these inhibitory effects, manuka honey
is known to reduce virulence, motility, and biofilm formation. With this increasing in vitro
dataset, we review the components and our mechanistic knowledge of manuka honey and how
manuka honey could potentially be utilized in the future to impact positively on the treatment
of microbial, resistant infections.
Keywords: Staphylococcus aureus, Pseudomonas aeruginosa, biofilm, antibiotic resistance
Introduction
The problem of antibiotic resistance
The ability of bacteria to adapt and become resistant to antibiotics has been recognized
by the scientific community for many decades. Staphylococcus aureus,1 Acinetobacter
baumannii,2
 and Enterococci species3
 are just some of the nosocomial pathogens
with increased antimicrobial resistance (AMR) that cause difficult-to-treat infections
worldwide. AMR is commonly accrued through genetic changes, which confer a more
resistant phenotype on the cell, or through the integration of the cell into a biofilm,
which can lead to a transient increase in tolerance to antibiotics of up to 1,000-fold.4
 The
biofilm phenotype is commonly found in urinary tract infections,5
 multi-species chronic
otitis media,6,7 and Pseudomonas aeruginosa infections in both burns8
 and the cystic
fibrosis lung.9
 The prolonged over- and misuse of antibiotics