Although it is becoming clear that the introduction of active surveillance followed by decolonization and contact isolation procedures can produce dramatic reductions in the incidence of hospital-acquired infections due to MRSA, adverse infection and mortality rates and high treatment costs associated with MRSA infections indicate that the development of more effective therapeutic and preventative options remains a priority. In particular, novel modalities that reduce or abrogate the emergence of antibiotic resistance mechanisms are highly desirable. Members of the flavonoid group of polyphenolic secondary metabolites substantially modify the properties of pathogenic bacteria in ways that could benefit the infected patient: they have been shown, such as inhibition of quorum sensing signalling mechanisms and secretion of virulence effectors that include toxins and enzymes associated with bacterial defense against host factors. Most importantly, some have the capacity to interfere with antibiotic resistance mechanisms, converting antibiotic resistant Gram-positive bacteria to a state of phenotypic susceptibility, and raising the possibility that druggable versions of these molecules could be used therapeutically alongside conventional antibiotics whose utility has been compromised by the dissemination of resistance genes. Indeed, use of the highly successful combination of the b-lactamase inhibitor clavulanic acid and the b-lactam agent amoxicillin, marketed as Augmentin,ON123300 is guided by such principles. Galloyl catechins such as -epicatechin gallate, epigallocatechin gallate and -catechin gallate are abundant components of the leaf of the green tea plant. They have negligible antibacterial activity but show the capacity, at relatively low concentrations, to reduce penicillinbinding protein 2a-mediated resistance to a wide range of blactam drugs. These molecules scavenge free radicals and show a strong tendency to partition into model lipid bilayers comprising single phospholipid species such as phosphatidylglycerol and phosphatidylethanolamine, penetrating deep into the hydrophobic core of the lipid palisade. Their nongalloyl homologs epicatechin,SD-06 epigallocatechin and catechin interact more superficially with PC and PE bilayers, localizing close to the phospholipid-water interface, and they do not have the capacity to modulate b-lactam resistance in MRSA. EC and EGC are, however, able to enhance the blactam-modifying potential of ECg and to increase the binding of ECg to staphylococcal cells. Further, EC and other nongalloyl catechins markedly increase the quantities of EGCg and ECg that are incorporated into artificial lipid bilayers. ECg has a higher affinity for membrane bilayers and a greater capacity to modulate b-lactam resistance than either EGCg or Cg, suggesting that a catechin-induced increase in the lipid order of the staphylococcal cytoplasmic membrane, producing tightly packed and extended acyl chains in the bilayer, is the primary event determining increased b-lactam susceptibility. Support for this view comes from the complex changes to the staphylococcal phenotype which accompanies abrogation of resistance. These include a reduction in peptidoglycan cross-linking, impairment of the processing and in situ activity of cell wall autolysins, a thickened cell wall and poor separation of daughter cells following division, a large reduction in D-alanyl esterification of cell wall teichoic acid, and loss of halotolerance; there is a high probability that this phenotype is due to alteration of the biophysical properties and function of the CM.