Chromosomally encoded systems involved in low level resistance of bacteria to different classes of antibiotics (mainly β-lactams, chloramphenicol, quinolones and tetracycline), disinfectants and in ...resistance to organic solvents have been the focus of considerable interest in recent years. The multiple antibiotic resistance (mar) locus ofEscherichia coli and Salmonella is perhaps the best described system involved in this type of resistance which is induced by MarA, the activator protein encoded by the marRAB locus. The mar -locus is reported to mediate resistance primarily by up-regulating efflux of some antibiotics, disinfectants and organic solvents via the AcrAB-TolC efflux pump and down regulating influx through Outer Membrane Protein F (OmpF). Whilst the level of antibiotic resistance conferred bymarRAB is only low level, there are increasing data to suggest that marRAB and related systems are important in clinical antibiotic resistance, possibly as a ‘stepping stone’ to higher levels of resistance. Other related systems include up-regulation of RobA, SoxS and AcrAB which give rise to a similar resistance phenotype to that conferred by up-regulation of MarA. The aim of this paper is to review the function and significance of the mar -locus and related systems with a particular focus on its implications in veterinary medicine.
Abstract
We present the first densely-sampled hydrographic survey of the Amundsen Sea Polynya (ASP) region, including a detailed characterization of its freshwater distributions. Multiple components ...contribute to the freshwater budget, including precipitation, sea ice melt, basal ice shelf melt, and iceberg melt, from local and non-local sources. We used stable oxygen isotope ratios in seawater (δ18O) to distinguish quantitatively the contributions from sea ice and meteoric-derived sources. Meteoric fractions were high throughout the winter mixed layer (WML), with maximum values of 2–3% (±0.5%). Because the ASP region is characterized by deep WMLs, column inventories of total meteoric water were also high, ranging from 10–13 m (±2 m) adjacent to the Dotson Ice Shelf (DIS) and in the deep trough to 7–9 m (±2 m) in shallower areas. These inventories are at least twice those reported for continental shelf waters near the western Antarctic Peninsula. Sea ice melt fractions were mostly negative, indicating net (annual) sea ice formation, consistent with this area being an active polynya. Independently determined fractions of subsurface glacial meltwater (as one component of the total meteoric inventory) had maximum values of 1–2% (±0.5%), with highest and shallowest maximum values at the DIS outflow (80–90 m) and in iceberg-stirred waters (150–200 m). In addition to these upwelling sites, contributions of subsurface glacial meltwater could be traced at depth along the ∼ 27.6 isopycnal, from which it mixes into the WML through various processes. Our results suggest a quasi-continuous supply of melt-laden iron-enriched seawater to the euphotic zone of the ASP and help to explain why the ASP is Antarctica’s most biologically productive polynya per unit area.
To determine the prevalence and types of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli occurring in pigs at slaughter in the UK in 2013. Caecal samples from 637 pigs, sampled via a ...UK-wide monitoring programme in 2013, were enriched overnight in buffered peptone water, before plating to CHROMagar CTX and Oxoid Brilliance ESBL agar. Presumptive ESBL-producing E. coli from both media were tested for ESBL phenotype using MAST ESβL ID discs. Isolates with an ESBL phenotype were examined for the presence of blaCTX-M, blaOXA, blaSHV and blaTEM genes using a multiplex PCR. All blaCTX-M and blaSHV genes identified by PCR were sequenced. A total of 23.4% (95% CI 19.2-27.6) of pigs were positive for ESBL-producing E. coli; 22% (95% CI 17.8-26.1) of the pigs carried E. coli producing CTX-M enzymes comprising enzyme types 1 (18.7% of pigs), 3 (0.2%), 14 (0.5%), 15 (1.4%), 27 (0.5%), 32 (0.5%) and 55 (0.3%) and 2.2% (95% CI 0.8-3.6) of the pigs carried E. coli producing SHV-12. Five pigs carried both CTX-M- and SHV-12-producing E. coli as different isolates. There were no statistically significant differences observed between the two medium types in terms of the proportions of each CTX-M enzyme type isolated. In this UK study, 23.4% of pigs were found to be positive for ESBL-producing E. coli using selective culture media. The use of two different commercially available ESBL isolation media was found to improve the detection of ESBL-producing E. coli.
Prior work on the signature whistles of bottlenose dolphins has focused on captive or temporarily restrained wild dolphins. Here we examine whistle production by free-ranging adult bottlenose ...dolphins. Whistles were recorded from each of 13 dolphins while they were restrained and free-swimming. Eleven of the 13 animals produced whistles while free-swimming that matched whistles produced while restrained. On average, 51% of the whistles an animal produced while free-swimming matched whistles recorded while that animal was gently restrained. Of those free-swimming whistles that matched restrained whistles, 76% matched signature whistles. A further analysis was conducted to determine the social contexts in which free-swimming dolphins produced signature whistles. An adult, allied male was most likely to produce signature whistles when voluntarily separated from his partner, and least likely to when together with his partner. These results suggest that wild bottlenose dolphins use signature whistles as contact calls, similar to captive dolphins. The majority of whistles produced by a pair of allied males in a consortship with a female were variant whistles. A final analysis showed that signature whistles appear individually distinctive, consistent with their use as contact calls, while variant whistles do not.
The signature whistle hypothesis states that dolphins produce highly stereotyped, individually distinctive whistles when in isolation. The presence of signature whistles has been called into question ...by recent studies proposing that dolphins produce a shared, simple upsweep whistle when in isolation, and that whistles produced by socializing dolphins are shared across individuals and social groups. This shared repertoire hypothesis suggests that when two animals produce the same whistle type, it is due to sharing the same common repertoire rather than one animal learning to produce the whistle of another. One difference between studies supporting or denying the existence of signature whistles is the method used to classify whistle types. We examined whistle production by 17 free-ranging bottlenose dolphins while temporarily restrained. We used both a quantitative comparison technique similar to that used to support the shared repertoire hypothesis and human judges to classify whistle types and quantify similarity between types. Contrary to recent studies that emphasize shared whistles, overall whistle sharing between isolated individuals was low (25%) and a simple upsweep did not account for the most common whistle type in half of the animals. Some species of birds, bats, and primates with stable social groups use vocal learning to converge over time to one common group distinctive call type. We examined whistle similarity between adult male dolphins that are partners in a close social alliance in order to test whether vocal learning may enable a similar vocal convergence. Whistle similarity was rated very high between partners and low between non-partners by both the quantitative technique and human observers. This suggests that as in songbirds and some other mammals, adult male bottlenose dolphins may use vocal learning to converge on similar whistles as they develop affiliative social relationships.
Several lines of evidence have led us to postulate that afferent vagal hyperactivity could be an important factor in the pathophysiology of the eating disorder bulimia nervosa. Ondansetron is a ...peripherally active antagonist of the serotonin receptor 5-HT3, and is marketed for prevention of vagally-mediated emesis caused by cancer chemotherapeutic agents. We investigated the effects of ondansetron on bulimic behaviours in patients with severe and chronic bulimia nervosa in a randomised, double-blind, placebo-controlled study.
We enrolled patients with severe bulimia nervosa (at least seven coupled binge/vomit episodes per week). The patients were otherwise healthy, their weight was normal, and they were not receiving medical or psychiatric treatment. During the first week of the study, patients recorded all eating-behaviour events to establish a baseline. In the second week, all patients received placebo, but were told that they were receiving either placebo or active drug. At the end of this single-blind phase, patients were randomly assigned placebo or ondansetron (24 mg daily) for a further 4 weeks. The primary outcome measure was the number of binge/vomit episodes per week. Data were analysed by intention to treat.
29 patients met the inclusion criteria, of whom 28 completed the baseline study, and 26 completed the single-blind placebo week. 12 patients were assigned placebo, and 14 ondansetron; one patient in the ondansetron group dropped out owing to accidental injury. During the 4th week of double-blind treatment, mean binge/vomit frequencies were 13·2 per week (SD 11·6) in the placebo group, versus 6·5 per week (3·9) in the ondansetron group (estimated difference 6·8 95% CI 4·0–9·5; p<0·0001). The ondansetron group also showed significant improvement, compared with the placebo group, in two secondary indicators of disease severity. The amount of time spent engaging in bulimic behaviours was decreased on average by 7·6 h per week in the ondansetron group, compared with 2·3 h in the placebo group (estimated difference 5·1 0·6–9·7). Similarly, the number of normal meals and snacks increased on average by 4·3 normal eating episodes without vomiting per week in the ondansetron group, compared with 0·2 in the placebo group (estimated difference 4·1 1·0–7·2).
The decrease in binge-eating and vomiting under ondansetron treatment was not achieved by compensatory changes in eating behaviour such as by a smaller number of binges of longer duration, or by not eating, or by binge-eating without vomiting. Instead, our findings indicate a normalisation of the physiological mechanism(s) controlling meal termination and satiation. Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission.
Recombinant adeno-associated serotype 2-based vectors (rAAV2) possess a number of theoretical advantages for cystic fibrosis (CF) gene therapy because they elicit little or no inflammatory response ...and generally result in stable expression. rAAV2 vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have previously been shown to mediate stable correction of the CF defect in CF bronchial epithelial cells and stable expression of CFTR in rabbit and nonhuman primate models. Here we report the results of the first trial initiated with rAAV in humans, a phase I study in 25 adult and adolescent CF patients with mild to moderate lung disease. Doses of the rAAV-CFTR vector (tgAAVCF) ranging from 3 x 10(1) to 1 x 10(9) replication units (RU), which is equivalent to approximately 6 x 10(4) to 2 x 10(12) DNase resistant particles (DRP), were administered to one side of the nose and to the superior segment of the lower lobe of the right lung. Several adverse events were noted prior to and/or after vector delivery, but most of them appeared to be related to the endogenous CF lung disease or a result of the bronchoscopic procedures. Only one of the serious events was judged to be possibly vector-related (based on temporal association), and this event was a pulmonary exacerbation very similar to several others experienced by the same subject in the three months preceding vector delivery. Vector shedding was minimal throughout the study, and serum-neutralizing antibodies were detected after vector delivery to subjects in the highest dosage cohorts. Gene transfer as measured by DNA polymerase chain reaction (PCR) was not observed until cohort 10 in nasal and bronchial epithelia. Sporadic low-level copy numbers suggested gene transfer of anywhere from 0.002 copies per cell up to 0.5 copies per cell was possible; however, DNA PCR was positive in lungs prior to direct dosing suggesting aspiration from the nasal dosing. These data indicate the need for continued evaluation of rAAV-CFTR vectors in additional clinical trials.
To detect and characterize Escherichia coli strains and pCT-like plasmids implicated in the dissemination of the CTX-M-14 gene in animals and humans, in England and Wales.
UK CTX-M-14-producing E. ...coli (n=70) from cattle (n=33), turkeys (n=9), sheep (n=2) and humans (n=26) were screened using multiplex PCR for the detection of a previously characterized plasmid, pCT. Isolates found to be carrying two or more pCT genetic markers were further analysed using PFGE. Their antimicrobial-resistance genes and virulence genes were also determined. These plasmids were transferred to Salmonella enterica serotype Typhimurium 26R and further examined for incompatibility type, genetic environment of the bla(CTX-M-14) gene, size, restriction fragment length polymorphism (RFLP) and nikB sequence.
The 25 E. coli isolates carrying pCT genetic markers generated 19 different PFGE profiles, and 23 isolates had different virulence and antimicrobial-resistance gene patterns. One isolate from cattle was a verotoxigenic E. coli ('VTEC'); the rest were commensal or extra-intestinal pathogenic E. coli. pCT-like plasmids with similar molecular characteristics (size, replicon type, RFLP pattern, pCT markers and genetic environment of the bla(CTX-M-14) gene) were detected in 21/25 of the field isolates, which comprised those from cattle (n=9), turkeys (n=8) and humans (n=4). All pCT-like plasmids were conjugative, and most were IncK (n=21) and had the same local genetic environment flanking the bla(CTX-M-14) gene (n=23). RFLP analysis demonstrated ≥ 75% similarity among most plasmids (n=22).
pCT-like plasmids were common vectors for horizontal dissemination of 30% of the bla(CTX-M-14) genes to different E. coli isolates from humans, cattle and turkeys.
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