Proteomic and genomic analysis of methicillin-resistant
Staphylococcus aureus (MRSA) exposed to manuka honey in vitro demonstrated
down-regulation of virulence markers
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.
No comments:
Post a Comment