In Vitro Assessment of the Synergy between Polymyxin B (PMB) and Polymyxin B Nonapeptide (PMBN) and Antibiotics on Biofilms from Diabetic Foot Infections

Background: The increasing resistance of Gram-negative bacteria isolated from nosocomial infections and chronic wounds, such as diabetic foot ulcers has renewed research interests in the use of polymyxins in the treatment of multidrug resistant infections. The added resistance conferred by biofilm development in such infections and the absence of novel antibiotics presuppose that polymyxins are the likely drugs of choice in spite of their nephrotoxicity. The effects of PMB and PMBN have been previously assessed on planktonic bacteria isolated from various infections. Methods: This current study assessed the synergy between a PMB/PMBN and two antibiotics (ceftazidime and levofloxacin) in an attempt to develop a strategy for biofilm disruption using the Minimum Biofilm Eradication Concentration Physiology and Genetic assay (MBEC™ P & G, Innovotech Inc, Edmonton, Alberta, Canada) according to manufacturer’s instructions. Klebsiella pneumoniae (K. pneumoniae) and Proteus mirabilis (P. mirabilis) biofilms of initial broth suspensions of 108 colony forming units per mL, cultivated on the pegs of the MBEC device were challenged with 5120 µg/mL of both ceftazidime and levofloxacin in a ten-fold dilution assay and in the presence of 100 and 500 µg/mL PMB and PMBN. Results: From table of results (Table 1), it can be deduced that both ceftazidime and levofloxacin are very effective in inhibiting biofilm development (as shown by percentage inhibition (PI)) when augmented with PMB and PMBN. This is about 100-fold increase in efficacy when compared to the antibiotics used on their own. The percentage reduction (PR) in biofilm was also increased considerably when PMB and PMBN concentrations were increased to 500 µg/mL. PMB was more effective than its less antibacterial derivative PMBN. Levofloxacin was also found to be more effective than ceftazidime when combined with both PMB and PMBN due to its enhanced cell-membrane permeability and as an anti-DNA replication uncoupling agent. Conclusion: The above results indicate that the synergy between antibiotics and cell membrane permeabilising agents may provide alternate strategies towards biofilm eradication

Enzymatic grafting: A novel approach to develop multifunctional materials of interest

Today more than 99% of plastics are petroleum-based because of the availability and cost of the raw material. The durability of disposed plastics contributes to the environmental problems as waste and their persistence in the environment causes deleterious effects on the ecosystem. Environmental pollution awareness and the demand for green technology have drawn considerable attention of both academia and industry into biodegradable polymers. In this regard green chemistry technology has the potential to provide solution to this issue. Enzymatic grafting has recently been the focus of green chemistry technologies due to the growing environmental concerns, legal restrictions, and increasing availability of scientific knowledge. Over the last several years, research covering various applications of robust enzymes like laccases and lipases has been increased rapidly, particularly in the field of polymer science, to graft multi-functional materials of interest. In principle, enzyme-assisted grafting may modify/impart a variety of functionalities to the grafted composites which individual materials fail to demonstrate on their own. The modified polymers through grafting have a bright future and their development is practically boundless. In the present study series of graft composites with poly(3-hydroxybutyrate) (P(3HB) as side chain and cellulose as a backbone polymer were successfully synthesised by introducing enzymatic grafting technique where laccase and lipase were used as model catalysts [1-3]. Subsequently, the resulting composites were removed from the casting surface under ambient environment and characterised by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD) in detail. Moreover, the thermo-mechanical behaviours of the grafted composites were investigated by differential scanning calorimetry (DSC) and dynamic mechanical analyser (DMA) measurements, respectively. In addition, hydrophobic and hydrophilic characteristics of the grafted polymers were studied through drop contour analysis using water contact angle (WCA). In comparison to the individual counterparts improvement was observed in the thermo- mechanical properties of the composites to varied extent. The tensile strength, elongation at break, and Young’s modulus values of the composites reached their highest levels in comparison to the films prepared with pure P(3HB) only which was too fragile to measure any of the above said characteristics. Interestingly, untreated P(3HB) was hydrophobic in nature and after lipase treatment P(3HB) and P(3HB)-EC-based graft composite attained higher level of hydrophilicity. This is a desired characteristic that enhances the biocompatibility of the materials for proper cell adhesion and proliferation therefore suggesting potential candidates for tissue engineering/bio-medical type applications [3]. The present research will be a first step in the biopolymer modification. To date no report has been found in literature explaining the laccase/lipase assisted grafting of P(3HB) [1-3]. The newly grafted composites exhibit unique functionalities with wider range of potential applications in bio-plastics, pharmaceutical, and cosmetics industries, tissue engineering, and biosensors. [1] H.M.N. Iqbal, G. Kyazze, T. Tron and T. Keshavarz, Cellulose 21, 3613-3621 (2014). [2] H.M.N. Iqbal, G. Kyazze, T. Tron and T. Keshavarz, Carbohydrate Polymers 113, 131-137 (2014). [3] H.M.N. Iqbal, G. Kyazze, T. Tron and T. Keshavarz, Polymer Chemistry In-Press, DOI: 10.1039/C4PY0 0857J (2014).

Context-aware Approach for Determining the Threshold Price in Name-Your-Own-Price Channels

Key feature of a context-aware application is the ability to adapt based on the change of context. Two approaches that are widely used in this regard are the context-action pair mapping where developers match an action to execute for a particular context change and the adaptive learning where a context-aware application refines its action over time based on the preceding action’s outcome. Both these approaches have limitation which makes them unsuitable in situations where a context-aware application has to deal with unknown context changes. In this paper we propose a framework where adaptation is carried out via concurrent multi-action evaluation of a dynamically created action space. This dynamic creation of the action space eliminates the need for relying on the developers to create context-action pairs and the concurrent multi-action evaluation reduces the adaptation time as opposed to the iterative approach used by adaptive learning techniques. Using our reference implementation of the framework we show how it could be used to dynamically determine the threshold price in an e-commerce system which uses the name-your-own-price (NYOP) strategy.