Methicillin-resistant Staphylococcus aureus (MRSA) is a global human health problem causing infections in both hospitals and the community. Companion animals, such as cats, dogs, and horses, are also ...frequently colonized by MRSA and can become infected. We sequenced the genomes of 46 multilocus sequence type (ST) 22 MRSA isolates from cats and dogs in the United Kingdom and compared these to an extensive population framework of human isolates from the same lineage. Phylogenomic analyses showed that all companion animal isolates were interspersed throughout the epidemic MRSA-15 (EMRSA-15) pandemic clade and clustered with human isolates from the United Kingdom, with human isolates basal to those from companion animals, suggesting a human source for isolates infecting companion animals. A number of isolates from the same veterinary hospital clustered together, suggesting that as in human hospitals, EMRSA-15 isolates are readily transmitted in the veterinary hospital setting. Genome-wide association analysis did not identify any host-specific single nucleotide polymorphisms (SNPs) or virulence factors. However, isolates from companion animals were significantly less likely to harbor a plasmid encoding erythromycin resistance. When this plasmid was present in animal-associated isolates, it was more likely to contain mutations mediating resistance to clindamycin. This finding is consistent with the low levels of erythromycin and high levels of clindamycin used in veterinary medicine in the United Kingdom. This study furthers the "one health" view of infectious diseases that the pathogen pool of human and animal populations are intrinsically linked and provides evidence that antibiotic usage in animal medicine is shaping the population of a major human pathogen.
Methicillin-resistant Staphylococcus aureus (MRSA) is major problem in human medicine. Companion animals, such as cats, dogs, and horses, can also become colonized and infected by MRSA. Here, we demonstrate that a shared population of an important and globally disseminated lineage of MRSA can infect both humans and companion animals without undergoing host adaptation. This suggests that companion animals might act as a reservoir for human infections. We also show that the isolates from companion animals have differences in the presence of certain antibiotic resistance genes. This study furthers the "one health" view of infectious diseases by demonstrating that the pool of MRSA isolates in the human and animal populations are shared and highlights how different antibiotic usage patterns between human and veterinary medicine can shape the population of bacterial pathogens.
A search has been performed for neutrinos from two sources, the hep reaction in the solar pp fusion chain and the νe component of the diffuse supernova neutrino background (DSNB), using the full ...dataset of the Sudbury Neutrino Observatory with a total exposure of 2.47 kton − years after fiducialization. The hep search is performed using both a single-bin counting analysis and a likelihood fit. We find a best-fit flux that is compatible with solar model predictions while remaining consistent with zero flux, and set a one-sided upper limit of Φhep < 30 × 103 cm−2 s−1 90% credible interval (CI). No events are observed in the DSNB search region, and we set an improved upper bound on the νe component of the DSNB flux of ΦνeDSNB < 19 cm−2 s−1 (90% CI) in the energy range 22.9 < Eν < 36.9 MeV.
Experimental tests of Lorentz symmetry in systems of all types are critical for ensuring that the basic assumptions of physics are well founded. Data from all phases of the Sudbury Neutrino ...Observatory, a kiloton-scale heavy water Cherenkov detector, are analyzed for possible violations of Lorentz symmetry in the neutrino sector. Such violations would appear as one of eight possible signal types in the detector: six seasonal variations in the solar electron neutrino survival probability differing in energy and time dependence and two shape changes to the oscillated solar neutrino energy spectrum. No evidence for such signals is observed, and limits on the size of such effects are established in the framework of the standard model extension, including 38 limits on previously unconstrained operators and improved limits on 16 additional operators. This makes limits on all minimal, Dirac-type Lorentz violating operators in the neutrino sector available for the first time.
Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the ...production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10−4 cm2/(g·μ), is measured to be 7.28±0.09(stat)−1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)−1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB.
Antibiotic resistance in bacterial pathogens threatens the future of modern medicine. One such resistant pathogen is methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to nearly ...all β-lactam antibiotics, limiting treatment options. Here, we show that a significant proportion of MRSA isolates from different lineages, including the epidemic USA300 lineage, are susceptible to penicillins when used in combination with β-lactamase inhibitors such as clavulanic acid. Susceptibility is mediated by a combination of two different mutations in the mecA promoter region that lowers mecA-encoded penicillin-binding protein 2a (PBP2a) expression, and in the majority of isolates by either one of two substitutions in PBP2a (E246G or M122I) that increase the affinity of PBP2a for penicillin in the presence of clavulanic acid. Treatment of S. aureus infections in wax moth and mouse models shows that penicillin/β-lactamase inhibitor susceptibility can be exploited as an effective therapeutic choice for 'susceptible' MRSA infection. Finally, we show that isolates with the PBP2a E246G substitution have a growth advantage in the presence of penicillin but the absence of clavulanic acid, which suggests that penicillin/β-lactamase susceptibility is an example of collateral sensitivity (resistance to one antibiotic increases sensitivity to another). Our findings suggest that widely available and currently disregarded antibiotics could be effective in a significant proportion of MRSA infections.
Using publicly available genomic data, combined with RT-PCR validation, we explore structural genomic variation for two major ion channels across insect classes. We have manually curated ryanodine ...receptor (RyR) and inositol 1,4,5-trisphosphate receptor (IP3R) ORFs and their corresponding genomic structures from 26 different insects covering major insect orders. We found that, despite high protein identity for both RyRs (>75%) and IP3Rs (~67%), the overall complexity of the gene structure varies greatly between different insect orders with the simplest genes (fewest introns) found in Diptera and the most complex in Lepidoptera. Analysis of intron conservation patterns indicated that the majority of conserved introns are found close to the 5′ end of the channels and in RyR around the highly conserved mutually exclusive splice site. Of the two channels the IP3Rs appear to have a less well conserved organisation with a greater overall number of unique introns seen between insect orders. We experimentally validated two of the manually curated ORFs for IP3Rs and confirmed an atypical (3799aa) IP3R receptor in Myzus persicae, which is approximately 1000 amino acids larger than previously reported for IP3Rs.
•Mapped the genomic structures of RyR and IP3R from 26 different insect species•Overall complexity of RyR and IP3R gene structure varies greatly between different insect orders.•Identified and experimentally validated an atypically large IP3R receptor in aphid species
Neutron production in giga electron volt–scale neutrino interactions is a poorly studied process. We have measured the neutron multiplicities in atmospheric neutrino interactions in the Sudbury ...Neutrino Observatory experiment and compared them to the prediction of a Monte Carlo simulation using genie and a minimally modified version of geant4. We analyzed 837 days of exposure corresponding to Phase I, using pure heavy water, and Phase II, using a mixture of Cl in heavy water. Neutrons produced in atmospheric neutrino interactions were identified with an efficiency of 15.3% and 44.3%, for Phases I and II respectively. The neutron production is measured as a function of the visible energy of the neutrino interaction and, for charged current quasielastic interaction candidates, also as a function of the neutrino energy. This study is also performed by classifying the complete sample into two pairs of event categories: charged current quasielastic and non charged current quasielastic, and νμ and νe. Results show good overall agreement between data and Monte Carlo for both phases, with some small tension with a statistical significance below 2σ for some intermediate energies.
PDF
