Non-genetic mechanisms communicating antibiotic resistance:rethinking strategies for antimicrobial drug design

Introduction: Infections by multidrug-resistant bacteria are of great concern worldwide. In many cases, resistance is not due to the presence of specific antibiotic-modifying enzymes, but rather associated with a general impermeability of the bacterial cell envelope. The molecular bases of this intrinsic resistance are not completely understood. Moreover, horizontal gene transfers cannot solely explain the spread of intrinsic resistance among bacterial strains. Areas covered: This review focuses on the increased intrinsic antibiotic resistance mediated by small molecules. These small molecules can either be secreted from bacterial cells of the same or different species (e.g., indole, polyamines, ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial cell milieu, whether in the environment, such as indole acetic acid and other plant hormones, or in human tissues and body fluids, such as polyamines. These molecules are metabolic byproducts that act as infochemicals and modulate bacterial responses toward antibiotics leading to increasing or decreasing resistance levels. Expert opinion: The non-genetic mechanisms of antibiotic response modulation and communication discussed in this review should reorient our thinking of the mechanisms of intrinsic resistance to antibiotics and its spread across bacterial cell populations. The identification of chemical signals mediating increased intrinsic antibiotic resistance will expose novel critical targets for the development of new antimicrobial strategies.

Timekeeping strategies operate independently from spatial and accuracy demands in beat-interception movements

The prevailing paradigm for researching sensorimotor synchronisation in humans involves finger tapping and temporal accuracy measures. However, many successful sensorimotor synchronisation actions require not only to be 'in time', but also to be in a predefined spatial position. Reaching this spatial position in many everyday actions often exceeds the average amplitude of a finger movement. The aim of this study is to address how people coordinate their movement to be in the right place at the right time when the scale of the movement varies. Does the scale of the movement and accuracy demands of the movement change the ability to accurately synchronise? To address these questions, a sensorimotor synchronisation task with three different inter-beat intervals, two different movement amplitudes and two different target widths was used. Our experiment demonstrated that people use different timing strategies-employing either a movement strategy (varying movement time) or a waiting strategy (keeping movement time constant) for large-scale movements. Those two strategies were found to be equally successful in terms of temporal accuracy and variability (spread of errors). With longer interval durations (2.5 and 3.5 s), variability of sensorimotor synchronisation performance increased (measured as the spread of errors). Analysing the data using the Vorberg and Wing (Handbook of perception and action. Academic Press, New York, pp 181-262, 1996) model shows a need to develop further existing timing models of sensorimotor synchronisation so that they could apply to large-scale movements, where different movement strategies naturally emerge.

Web-based social movements contesting marketing strategy: Mobilization of multiple actors and rhetorical strategies

Previous studies suggest that marketing strategy is developed and used to mobilise and configure the actions of firm actors, creating a set of stabilising activities focused on the firm–customer dyad. Destabilising forces precipitated by the Internet and associated digital technologies involving contention and disruption by multiple actors are much less prevalent in the marketing literature. The central point we advance is that rather than marketing strategy being a controlled and stabilising force for firms in their relationships with customers, it can often lead to socially produced spaces where consumers and, importantly, other multiple actors form a social movement to actively attempt to destabilise it and contest its legitimacy. Using an innovative research approach, the findings of this study show how social movements proactively enrol and mobilise a wide range of relevant actors into a network of influence. Critical to this are rhetorical strategies, acting as important levers in attempts to destabilise and delegitimise a dominant firm's marketing strategy.

Treatment of lung infection in patients with cystic fibrosis:Current and future strategies

In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic therapy for the major pathogens in CF airways, including prophylaxis against infection, eradication of early infection, suppression of chronic infection, and the treatment of infective exacerbations. We outline measures to optimize maintenance treatment for infection in the light of novel antibiotic drug formulations. We discuss new developments in culture-independent microbiological diagnostic techniques and the use of tools for monitoring the success of antibiotic treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment in CF patients are discussed.

Minimizing side reactions in chemoenzymatic dynamic kinetic resolution: organometallic and material strategies

Chemoenzymatic dynamic kinetic resolution (DKR) of rac-1-phenyl ethanol into R-1-phenylethanol acetate was investigated with emphasis on the minimization of side reactions. The organometallic hydrogen transfer (racemization) catalyst was varied, and this was observed to alter the rate and extent of oxidation of the alcohol to form ketone side products. The performance of highly active catalyst [(pentamethylcyclopentadienyl) IrCl2(1-benzyl,3-methyl-imidazol-2-ylidene)] was found to depend on the batch of lipase B used. The interaction between the bio- and chemo-catalysts was reduced by employing physical entrapment of the enzyme in silica using a sol-gel process. The nature of the gelation method was found to be important, with an alkaline method preferred, as an acidic method was found to initiate a further side reaction, the acid catalyzed dehydration of the secondary alcohol. The acidic gel was found to be a heterogeneous solid acid.

Arsenic as a food chain contaminant:mechanisms of plant uptake and metabolism and mitigation strategies

Arsenic (As) is an environmental and food chain contaminant. Excessive accumulation of As, particularly inorganic arsenic (As(i)), in rice (Oryza sativa) poses a potential health risk to populations with high rice consumption. Rice is efficient at As accumulation owing to flooded paddy cultivation that leads to arsenite mobilization, and the inadvertent yet efficient uptake of arsenite through the silicon transport pathway. Iron, phosphorus, sulfur, and silicon interact strongly with As during its route from soil to plants. Plants take up arsenate through the phosphate transporters, and arsenite and undissociated methylated As species through the nodulin 26-like intrinsic (NIP) aquaporin channels. Arsenate is readily reduced to arsenite in planta, which is detoxified by complexation with thiol-rich peptides such as phytochelatins and/or vacuolar sequestration. A range of mitigation methods, from agronomic measures and plant breeding to genetic modification, may be employed to reduce As uptake by food crops.