Clinically Relevant Growth Conditions Alter Acinetobacter baumannii Antibiotic Susceptibility and Promote Identification of Novel Antibacterial Agents

Biological processes that govern bacterial proliferation and survival in the host-environment(s) are likely to be vastly different from those that are required for viability in nutrient-rich laboratory media. Consequently, growth-based antimicrobial screens performed in conditions modeling aspects of bacterial disease states have the potential to identify new classes of antimicrobials that would be missed by screens performed in conventional laboratory media. Accordingly, we performed screens of the Selleck library of 853 FDA approved drugs for agents that exhibit antimicrobial activity toward the Gram-negative bacterial pathogen Acinetobacter baumannii during growth in human serum, lung surfactant, and/or the organism in the biofilm state and compared those results to that of conventional laboratory medium. Results revealed that a total of 90 compounds representing 73 antibiotics and 17 agents that were developed for alternative therapeutic indications displayed antimicrobial properties toward the test strain in at least one screening condition. Of the active library antibiotics only four agents, rifampin, rifaximin, ciprofloxacin and tetracycline, exhibited antimicrobial activity toward the organism during all screening conditions, whereas the remainder were inactive in ≥ 1 condition; 56 antibiotics were inactive during serum growth, 25 and 38 were inactive toward lung surfactant grown and biofilm-associated cells, respectively, suggesting that subsets of antibiotics may outperform others in differing infection settings. Moreover, 9 antibiotics that are predominantly used for the treatment Gram-positive pathogens and 10 non-antibiotics lacked detectable antimicrobial activity toward A. baumannii grown in conventional medium but were active during ≥ 1 alternative growth condition(s). Such agents may represent promising anti-Acinetobacter agents that would have likely been overlooked by antimicrobial whole cell screening assays performed in traditional laboratory screening media.     

The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties

Introduction  

The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia (FM) patients. Over the last 18 years, since the publication of the original FIQ, several deficiencies have become apparent and the cumbersome scoring algorithm has been a barrier to widespread clinical use. The aim of this paper is to describe and validate a revised version of the FIQ: the FIQR.     

Reversible Control by Vitamin D of Granulocytes and Bacteria in the Lungs of Mice: An Ovalbumin-Induced Model of Allergic Airway Disease

Vitamin D may be essential for restricting the development and severity of allergic diseases and asthma, but a direct causal link between vitamin D deficiency and asthma has yet to be established. We have developed a ‘low dose’ model of allergic airway disease induced by intraperitoneal injection with ovalbumin (1 µg) and aluminium hydroxide (0.2 mg) in which characteristics of atopic asthma are recapitulated, including airway hyperresponsiveness, antigen-specific immunoglobulin type-E and lung inflammation. We assessed the effects of vitamin D deficiency throughout life (from conception until adulthood) on the severity of ovalbumin-induced allergic airway disease in vitamin D-replete and -deficient BALB/c mice using this model. Vitamin D had protective effects such that deficiency significantly enhanced eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male but not female mice. Vitamin D also suppressed the proliferation and T helper cell type-2 cytokine-secreting capacity of airway-draining lymph node cells from both male and female mice. Supplementation of initially vitamin D-deficient mice with vitamin D for four weeks returned serum 25-hydroxyvitamin D to levels observed in initially vitamin D-replete mice, and also suppressed eosinophil and neutrophil numbers in the bronchoalveolar lavage fluid of male mice. Using generic 16 S rRNA primers, increased bacterial levels were detected in the lungs of initially vitamin D-deficient male mice, which were also reduced by vitamin D supplementation. These results indicate that vitamin D controls granulocyte levels in the bronchoalveolar lavage fluid in an allergen-sensitive manner, and may contribute towards the severity of asthma in a gender-specific fashion through regulation of respiratory bacteria.     

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity^1-5. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions.Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures^1,6,7. We developed a new model¹ which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (K_d) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections.     

The Role of Habitat Complexity in Community Development Is Mediated by Resource Availability

Habitat complexity strongly affects the structure and dynamics of ecological communities, with increased complexity often leading to greater species diversity and abundance. However, habitat complexity changes as communities develop, and some species alter their environment to themselves provide habitat for other species. Most experimental studies manipulate basal substrate complexity, and while the importance of complexity likely changes during community development, few studies have examined the temporal dynamics of this variable. We used two experiments to quantify the importance of basal substrate complexity to sessile marine invertebrate community development through space and time. First, we compared effects of substrate complexity at 70 sites across ten estuaries. Sites differed in recruitment and community development rates, and after three months provided spatial variation in community development stage. Second, we tested for effects of substrate complexity at multiple times at a single site. In both experiments, complexity affected marine sessile invertebrate community composition in the early stages of community development when resource availability was high. Effects of complexity diminished through time as the amount of available space (the primary limiting resource) declined. Our work suggests the presence of a bare-space threshold, at which structural complexity of the basal substrate is overwhelmed by secondary biotic complexity. This threshold will be met at different times depending on local recruitment and growth rates and is likely to vary with productivity gradients.     

The importance of scale in comparative microbiome research: New insights from the gut and glands of captive and wild lemurs

Research on animal microbiomes is increasingly aimed at determining the evolutionary and ecological factors that govern host–microbiome dynamics, which are invariably intertwined and potentially synergistic. We present three empirical studies related to this topic, each of which relies on the diversity of Malagasy lemurs (representing a total of 19 species) and the comparative approach applied across scales of analysis. In Study 1, we compare gut microbial membership across 14 species in the wild to test the relative importance of host phylogeny and feeding strategy in mediating microbiome structure. Whereas host phylogeny strongly predicted community composition, the same feeding strategies shared by distant relatives did not produce convergent microbial consortia, but rather shaped microbiomes in host lineage‐specific ways, particularly in folivores. In Study 2, we compare 14 species of wild and captive folivores, frugivores, and omnivores, to highlight the importance of captive populations for advancing gut microbiome research. We show that the perturbational effect of captivity is mediated by host feeding strategy and can be mitigated, in part, by modified animal management. In Study 3, we examine various scent‐gland microbiomes across three species in the wild or captivity and show them to vary by host species, sex, body site, and a proxy of social status. These rare data provide support for the bacterial fermentation hypothesis in olfactory signal production and implicate steroid hormones as mediators of microbial community structure. We conclude by discussing the role of scale in comparative microbial studies, the links between feeding strategy and host–microbiome coadaptation, the underappreciated benefits of captive populations for advancing conservation research, and the need to consider the entirety of an animal's microbiota. Ultimately, these studies will help move the field from exploratory to hypothesis‐driven research.     

Understanding Perceptions of Climate Change,Priorities, and Decision-Making among Municipalities in Lima,Peru to Better Inform Adaptation and Mitigation Planning

Climate change poses multiple risks to the population of Lima, the largest city and capital of Peru, located on the Pacific coast in a desert ecosystem. These risks include increased water scarcity, increased heat, and the introduction and emergence of vector-borne and other climate sensitive diseases. To respond to these threats, it is necessary for the government, at every level, to adopt more mitigation and adaptation strategies. Here, focus groups were conducted with representatives from five Lima municipalities to determine priorities, perception of climate change, and decision-making processes for implementing projects within each municipality. These factors can affect the ability and desire of a community to implement climate change adaptation and mitigation strategies. The results show that climate change and other environmental factors are of relatively low priority, whereas public safety and water and sanitation services are of highest concern. Perhaps most importantly, climate change is not well understood among the municipalities. Participants had trouble distinguishing climate change from other environmental issues and did not fully understand its causes and effects. Greater understanding of what climate change is and why it is important is necessary for it to become a priority for the municipalities. Different aspects of increased climate change awareness seem to be connected to having experienced extreme weather events, whether related or not to climate change, and to higher socioeconomic status.     

Opinions of UK Rescue Shelter and Rehoming Center Workers on the Problems Facing Their Industry

Animal shelters exist worldwide to care for and rehome unwanted or straying pets. Previous studies have examined why owners breed unwanted animals, or relinquish their pets to shelters. However, the views of shelter workers, who receive and care for these animals, have previously been largely unexplored. The aim of this study was to investigate the perceptions of animal shelter workers on the problems facing their industry. A sampling frame was constructed, consisting of every identified shelter in the UK, and a postal questionnaire sent to each. This included two open questions, soliciting respondents’ views on their biggest problems, and inviting further comments. A total of 661 respondents replied to at least one question. Thematic analysis on the free text content was carried out, and basic and global themes identified. Respondents’ main concerns centered on a mismatch between the continuous demand for their services and their limited resources, which has worsened during the recent financial crisis. Respondents perceived a need for increased public awareness of the commitment involved in keeping a pet, and of controlling breeding by neutering. Points of intervention, such as education programs, were suggested. Coordinating efforts with others, including local authorities, landlords, and housing associations, and a potential role for veterinary professionals working in shelter medicine were all explored by respondents. Rehoming organizations play an important role in the management of pet overpopulation, and the views and beliefs of their workers form an important contribution to the dialogue surrounding this issue. Consideration of these perspectives may suggest alternative routes to address underlying causes and management of pet overpopulation.