Selective conditions for a multidrug resistance plasmid depend on the sociality of antibiotic resistance"

Multidrug resistance (MDR) plasmids frequently carry antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show here that the antibiotic concentrations selecting for the RK2 plasmid inEscherichia colidepend upon the sociality of the drug resistance: the selection for selfish drug resistance (efflux pump) occurred at very low drug concentrations, just 1.3% of the MIC of the plasmid-free antibiotic-sensitive strain, whereas selection for cooperative drug resistance (modifying enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain

Portrait methodology and educational leadership : putting the person first

This article describes a variant on a methodological approach which provides ways of developing educational leaders' understandings of themselves and their situation through the production of individually written 'portraits' which focus upon the individuals' personal concerns and issues. It describes the process undertaken in forming a particular application of this approach, which is characterised by being highly private, highly personal and conducted by peers, rather than by others in a hierarchical relationship, to produce a picture of a person's concerns at one moment in time. It examines a number of possible criticisms, before arguing that there are a number of distinct benefits to its adoption. A description is provided of how such a methodology can be translated into a useful tool that provides individuals with the non-judgemental space to reflect upon themselves and their performance, and to develop supportive networks of peers who can help to sustain them in their job. This approach then could not only help remediate current issues of recruitment and retention to leadership positions, it could also provide private development space in societies and educational systems increasingly characterised by surveillance and public criticism of performance. Finally, whilst this article focuses upon the use of portraits for educational leaders, it is suggested that it is a technique that could be used by virtually anyone in order to create space for private reflection

The Sociality and Evolution of Plasmid-Mediated Antimicrobial Resistance

Overuse and misuse of antibiotics has led to the global spread of antimicrobial resistance, threatening our ability to treat bacterial infections. The horizontal acquisition of multidrug resistance (MDR) plasmids, from other bacterial lineages, has been instrumental in spreading resistance. Newly acquired plasmids are often poorly adapted to hosts causing intragenomic conflicts, reducing the competitiveness of plasmid-carrying strains. Costs can be overcome by positive selection for plasmid-encoded adaptive traits in the short-term, or ameliorated by compensatory evolution in the long-term. How the selection and adaptation of MDR plasmids varies with antibiotic treatment remains unclear. First, I demonstrate that the selective conditions for the maintenance of an MDR plasmid are dependent upon the sociality of resistance it encodes. Selection for efflux of antibiotics, a selfish trait, occurred at very low concentrations of antibiotic, far below the minimum inhibitory concentration of sensitive plasmid-free strain. In contrast, selection for inactivation of antibiotics, a cooperative trait, increased the amount of antibiotic required to select for the MDR plasmid, allowing sensitive plasmid-free bacteria to survive high levels of antibiotic. These selection dynamics were only accurately predicted when mathematical models included the mechanistic details of antibiotic resistance. Secondly, I show that the trajectory of evolution following MDR plasmid acquisition varies with antibiotic treatment. Tetracycline treatment favoured a distinct coevolutionary trajectory of chromosomal resistance mutations coupled with plasmid mutations impairing plasmid-borne resistance. This led to high-level, low-cost antibiotic resistance, but also produced an integrated genome of co-dependent replicons that may limit the onward spread of co-adapted MGEs to other lineages. This evolutionary trajectory was strikingly repeatable across independently evolving populations despite the emergence of multiple competing lineages within populations. The results presented here demonstrate that the interaction between positive selection and compensatory evolution can help to explain the persistence of MDR plasmids in the clinic and the environment

Spatial organisation of expanding bacterial colonies is affected by contact-dependent growth inhibition

Identifying how microbes are able to manipulate, survive and thrive in complex multispecies communities has expanded our understanding of how microbial ecosystems impact human health and the environment. The ability of bacteria to negatively affect neighbours, through explicit toxin delivery systems, provides them with an opportunity to manipulate the composition of growing microbial communities. Contact-dependent inhibition (CDI) systems (a Type Vb secretion system) are a distinct subset of competition systems whose contribution to shaping the development of spatially-structured bacterial communities are yet to be fully understood. Here we compare the impact of different CDI systems, at both the single cell and population level, to determine the key drivers of CDI-mediated competition within spatially-structured bacterial populations. Through an iterative approach using both an Escherichia coli experimental system and computational modelling, we show that CDI systems have subtle and system-specific effects at the single cell level, generating single cell wide boundaries between CDI-expressing inhibitor cells and their neighbouring targets. Despite the subtle effects of CDI at a single cell level, CDI systems greatly diminished the ability of susceptible targets to expand their range during colony growth. The inoculum density of the population, together with the CDI system-specific variables of the speed of inhibition after contact and biological cost of CDI, strongly affects CDI-mediated competition. In contrast, the magnitude of the toxin-induced growth retardation of target cells only weakly impacts the composition of the population. Our work reveals how distinct CDI systems can differentially affect the composition and spatial arrangement of bacterial populations

Ecology and evolution of antimicrobial resistance in bacterial communities

Accumulating evidence suggests that the response of bacteria to antibiotics is significantly affected by the presence of other interacting microbes. These interactions are not typically accounted for when determining pathogen sensitivity to antibiotics. In this perspective, we argue that resistance and evolutionary responses to antibiotic treatments should not be considered only a trait of an individual bacteria species but also an emergent property of the microbial community in which pathogens are embedded. We outline how interspecies interactions can affect the responses of individual species and communities to antibiotic treatment, and how these responses could affect the strength of selection, potentially changing the trajectory of resistance evolution. Finally, we identify key areas of future research which will allow for a more complete understanding of antibiotic resistance in bacterial communities. We emphasise that acknowledging the ecological context, i.e. the interactions that occur between pathogens and within communities, could help the development of more efficient and effective antibiotic treatments

Non-antibiotic pharmaceuticals are toxic against <i>Escherichia coli</i> with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear. We aimed to assess whether non-antibiotic pharmaceuticals and other compounds produced by pharmaceutical plants have inherent toxicity, and whether long-term exposure might result in significant genetic changes or select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, metformin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The compounds did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these compounds, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet.

The tsetse fly is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo This has been used subsequently to analyze in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl-d-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence on l-glutamate as a source of carbon and nitrogen and by the ability to rescue a predicted l-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution of S. glossinidius to exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.IMPORTANCE Human African trypanosomiasis is caused by the Trypanosoma brucei parasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential for T. brucei life cycle progression and transmission. The tsetse's mutualistic endosymbiont Sodalis glossinidius has a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model of S. glossinidius metabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects of S. glossinidius metabolism. We present S. glossinidius as uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally, S. glossinidius has adapted to the tsetse's obligate symbiont Wigglesworthia glossinidia by scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet.

The tsetse fly is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo This has been used subsequently to analyze in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl-d-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence on l-glutamate as a source of carbon and nitrogen and by the ability to rescue a predicted l-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution of S. glossinidius to exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.IMPORTANCE Human African trypanosomiasis is caused by the Trypanosoma brucei parasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential for T. brucei life cycle progression and transmission. The tsetse's mutualistic endosymbiont Sodalis glossinidius has a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model of S. glossinidius metabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects of S. glossinidius metabolism. We present S. glossinidius as uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally, S. glossinidius has adapted to the tsetse's obligate symbiont Wigglesworthia glossinidia by scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission

Educational Leadership for a More Sustainable World

Educational Leadership for a More Sustainable World argues that current crises in educational policies and practice, including the recruitment and retention of educational leaders, ultimately derive from the interactions between four key challenges which also underpin current global and societal issues of sustainability:A culture of consumptionGlobal energy demandsClimate changeEmerging population patternsMike Bottery argues that problems in dealing with these four global challenges, as well as many crises in education, are in large part due to a failure to appreciate their complex interactions and effects, and of the need for sufficiently complex responses. The result is that many policies in many areas hinder rather than facilitate appropriate solutions.However, by showing that the dynamics of crises in educational sustainability have many similarities to those of global systems, this book argues that the adoption of a number of core practices and values can help educational leaders develop greater sustainability, not only in their own area of activity but can also help them make a valuable contribution to greater sustainability at the global level as well

Leadership, sustainability and ethics

This chapter is concerned with what educational leaders can lear about the ethics of their practice from a study of environmental systems. It examiners three sources for such learning. One source is from an understanding of the epistemology of these two systems, particular from a gerater understanding of the complexity of actions., as well as a necesarily greater provisionality of judgments than is normally recognised. A second source of ethical learning stems fromexamining when these two systems get into trouble, for both education and the environment suffer from a numbr of similar kinds of stressors, and similar kinds of crisis points. A final source of ethical learning derives from the fact that both systems appear to benefit from simmilar prescriptions for remediation and greater sustainability