J Antimicrob Chemother, 2013 Oct 31
OBJECTIVES:
Methicillin-resistant Staphylococcus aureus (MRSA) is an
important pathogen. Its resistance to multiple antibiotics and its prevalence
in healthcare establishments make it a serious threat to human health that
requires novel interventions. Manuka honey is a broad-spectrum antimicrobial
agent that is gaining acceptance in the topical treatment of wounds. Because
its mode of action is only partially understood, proteomic and genomic analysis
was used to investigate the effects of manuka honey on MRSA at a molecular
level.
METHODS:
Two-dimensional gel electrophoresis with dual-channel
imaging was combined with matrix-assisted laser desorption ionization-time of
flight mass spectrometry to determine the identities of differentially
expressed proteins. The expression of the corresponding genes was investigated
by quantitative PCR. Microarray analysis provided an overview of alterations in
gene expression across the MRSA genome.
RESULTS:
Genes with increased expression following exposure to manuka
honey were associated with glycolysis, transport and biosynthesis of amino
acids, proteins and purines. Those with decreased expression were involved in
the tricarboxylic acid cycle, cell division, quorum sensing and virulence. The
greatest reductions were seen in genes conferring virulence (sec3, fnb, hlgA,
lip and hla) and coincided with a down-regulation of global regulators, such as
agr, sae and sarV. A model to illustrate these multiple effects was constructed
and implicated glucose, which is one of the major sugars contained in honey.
CONCLUSIONS:
A decreased expression of virulence genes in MRSA will
impact on its pathogenicity and needs to be investigated in vivo.
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