In recent years multi-drug resistant (MDR) strains have disseminated worldwide [2]. A. baumannii is intrinsically resistant to many antimicrobial compounds but also has a remarkable capacity AUY-922 research buy to capture and sustain antimicrobial resistance determinants [2]. MDR strains are able to evade the effects of most antibiotics through a combination of enzymatic inactivation (β-lactamases, aminoglycoside modifying enzymes), impermeability (porin loss), chromosomal mutations and active efflux of drugs.

Due to the lack of new synthetic antimicrobials in development for the treatment of MDR Gram-negative infections, attention is increasingly focused on natural compounds either as stand-alone or adjunctive therapies. These include plant polyphenols such as those found in tea e.g. catechins and spices e.g. curcumin. Curcumin (CCM) is a diphenolic compound, commonly used in the form of turmeric throughout central

and Eastern Asia as a spice and/or colouring agent in foodstuffs and textiles. A number of potential health benefits have been associated with CCM including anti-neoplastic, anti-inflammatory and anti-oxidant effects [3]. Studies have also revealed that CCM may have antimicrobial activity against Tideglusib cell line both Gram-positive (Streptococcus mutans) [4] and Gram-negative bacteria (Helicobacter pylori) [5]. The antibacterial effects of CCM have also been shown to be affected when BTK inhibitor solubility dmso combined with other antimicrobials. Synergy has been observed when combined with oxacillin and ampicillin against meticillin-resistant Staphylococcus aureus [6] but antagonism when used with ciprofloxacin against Salmonella typhi [7]. Epigallocatechin-3-gallate (EGCG) is a polyphenol found in green tea, which like CCM, has been linked with

health benefits and has significant antimicrobial activity against some MDR pathogens [8, 9]. Previous studies have also shown that A. baumannii is inhibited by EGCG at concentrations between 78-625 μg/mL [10] and that the compound may act as an inhibitor of chromosomal penicillinase in S. aureus [11]. The potential for polyphenols to be used together against MDR Gram-negative bacteria was demonstrated previously, whereby potent synergy was observed when epicatechin was combined with theaflavin against A. baumannii and Stenotrophomonas 6-phosphogluconolactonase maltophilia [12]. The bioavailability of natural compounds such as polyphenols and curcumin has been previously investigated and found to be in some cases their ‘Achilles heel’. Several studies have reported that although polyphenols penetrate effectively into various tissues [13] their bioavailability is poor [14] and it is difficult to achieve adequate concentrations for antimicrobial activity in mammalian models [15]. This may be a facet of their ability to bind to proteins [16] although many polyphenols are also rapidly metabolised in mammals [17].