Comparing the selective and co-selective effects of different antimicrobials in bacterial communities

This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this recordBacterial communities are exposed to a cocktail of antimicrobial agents, including antibiotics, heavy metals and biocidal antimicrobials such as quaternary ammonium compounds (QACs). The extent to which these compounds may select or co-select for antimicrobial resistance (AMR) is not fully understood. In this study, human associated, wastewater derived, bacterial communities were exposed to either benzalkonium chloride (BAC), ciprofloxacin or trimethoprim at sub-point of use concentrations for one week, in order to determine selective and co-selective potential. Metagenome analyses were performed to determine effects on bacterial community structure and prevalence of antibiotic resistance genes (ARGs) and metal or biocide resistance genes (MBRGS). Ciprofloxacin had the greatest co-selective potential, significantly enriching for resistance mechanisms to multiple antibiotic classes. Conversely, BAC exposure significantly reduced relative abundance of ARGs and MBRGS, including the well characterised qac efflux genes. However, BAC exposure significantly impacted bacterial community structure. This suggests BAC and potentially other QACs did not play as significant a role in co-selection for AMR relative to antibiotics such as ciprofloxacin at below point of use concentrations in this study. This approach can be used to identify priority compounds for further study, to better understand evolution of AMR in bacterial communities exposed to sub-point of use concentrations of antimicrobials.Natural Environment Research Council (NERC)Biotechnology and Biological Sciences Research Council (BBSRC

Inhibition of Poly(ADP-Ribose) polymerase enhances the toxicity of 131I-Metaiodobenzylguanidine/Topotecan combination therapy to cells and xenografts that express the noradrenaline transporter

Targeted radiotherapy using [131I]meta-iodobenzylguanidine ([131I]MIBG) has produced remissions in some neuroblastoma patients. We previously reported that combining [131I]MIBG with the topoisomerase I (Topo-I) inhibitor topotecan induced long-term DNA damage and supra-additive toxicity to NAT-expressing cells and xenografts. This combination treatment is undergoing clinical evaluation. This present study investigated the potential of PARP-1 inhibition, in vitro and in vivo, to further enhance [131I]MIBG/topotecan efficacy

Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities

This is the final version of the article. Available from American Society for Microbiology via the DOI in this record.Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for blaCTX-M genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner.Aimee K. Murray was supported by a BBSRC/AZ CASE Studentship, BB/L502509/1. Lihong Zhang was supported by Natural Environment Research Council grant NE/ M011259/1. Chemical quantification was performed at the University of Exeter Streatham Campus by Maciek Trnzadel and Malcolm Hetheridge, cofunded by Astra Zeneca Global SHE and the University of Exeter

Staphylococcus cornubiensis sp. nov., a member of the Staphylococcus intermedius Group (SIG)

This is the author accepted manuscript. The final version is available from Microbiology Society via the DOI in this recordWe here describe a novel species in the Staphylococcus intermedius Group (SIG) which is phenotypically similar to Staphylococcus pseudintermedius but is genomically distinct from it and other SIG members, with an average nucleotide identity of 90.2 % with its closest relative S. intermedius. The description of Staphylococcus cornubiensis sp. nov. is based on strain NW1T (=NCTC 13950T=DSM 105366T) isolated from a human skin infection in Cornwall, UK. Although pathogenic, NW1T carries no known virulence genes or mobilizable antibiotic resistance genes and further studies are required to assess the prevalence of this species in humans as well as its potential presence in companion animals.This work was supported by the Wellcome Trust (grant WT 098051). We acknowledge BBSRC/MRC funding (grant MR/N007174/1) enabling discounted sequencing through the microbesNG program

The variability and seasonality of the environmental reservoir of Mycobacterium bovis shed by wild European badgers

This is the final version of the article. Available from the publisher via the DOI in this record.The incidence of Mycobacterium bovis, the causative agent of bovine tuberculosis, has been increasing in UK cattle herds resulting in substantial economic losses. The European badger (Meles meles) is implicated as a wildlife reservoir of infection. One likely route of transmission to cattle is through exposure to infected badger urine and faeces. The relative importance of the environment in transmission remains unknown, in part due to the lack of information on the distribution and magnitude of environmental reservoirs. Here we identify potential infection hotspots in the badger population and quantify the heterogeneity in bacterial load; with infected badgers shedding between 1 × 10(3)- 4 × 10(5) M. bovis cells g(-1) of faeces, creating a substantial and seasonally variable environmental reservoir. Our findings highlight the potential importance of monitoring environmental reservoirs of M. bovis which may constitute a component of disease spread that is currently overlooked and yet may be responsible for a proportion of transmission amongst badgers and onwards to cattle.We acknowledge funding from Defra, H.C.K. was in receipt of a BBSRC DTG studentship and E.M.W. and O.C. acknowledge support from BBSRC for collaboration with Eamonn Gormley, UCD. We are also grateful to the APHA field team at Woodchester Park for support during fieldwork, and to Defra who fund the long-term stud

Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma

Background and Purpose: State-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma. Materials and Methods: The risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues). The risk ratio (RR) between radiotherapy modalities and lifetime absolute risks (LAR) were reported for twenty abdominal neuroblastoma patients (median, 4y; range, 1-9y) historically treated with 3D-CRT that were also retrospectively replanned for IMAT and PBS-PT. Results: The risk of SMN due to primary radiation was reduced in PBS-PT against 3D-CRT and IMAT for most patients and organs. The RR across all organs ranged from 0.38 ± 0.22 (bladder) to 0.98 ± 0.04 (CNS) between PBS-PT and IMAT, and 0.12 ± 0.06 (rectum and bladder) to 1.06 ± 0.43 (bone) between PBS-PT and 3D-CRT. The LAR for most organs was within 0.01–1% (except the colon) with a cumulative risk of 21 ± 13%, 35 ± 14% and 35 ± 16% for PBS-PT, IMAT and 3D-CRT, respectively. Conclusions: PBS-PT was associated with the lowest risk of radiation-induced SMN compared to IMAT and 3D-CRT in abdominal neuroblastoma treatment. Other clinical endpoints and plan robustness should also be considered for optimal plan selection

Consumo de Savia por Melanerpes cactorum y su Rol en la Estructuración de Ensambles de Aves en Bosques Secos

The White-fronted Woodpecker (Melanerpes cactorum) drills holes in branches and trunks to feed on sap flows, providing an energy-rich food resource for other birds. Here we describe ecological and behavioral traits of the White-fronted Woodpecker related to its sap-feeding habits in the semiarid Chaco of Argentina and explore the structure of the avian assemblage in relation to the sap resource. Sap consumption by the White-fronted Woodpecker and other sap-feeding species was strongly seasonal and positively associated with periods of resource scarcity. The White-fronted Woodpecker actively defended the sap wells from smaller birds. Specialist and facultative nectarivores that assimilate sucrose at a high rate represented an important proportion of sap-feeding birds. In this system of woodpecker, sap, and other sap-feeding species, each species’ consumption depends on its physiological and behavioral characteristics as well as on the availability of other food in the surrounding environment.Melanerpes cactorum perfora ramas y troncos de árboles y arbustos para consumir la savia que fluye de las perforaciones, posibilitando a otras especies de aves el acceso a un recurso de alto contenido energé- tico. En este estudio describimos rasgos de la historia natural de M. cactorum relacionados con su alimentación en el Chaco semiárido de Argentina e investigamos la estructuración de ensambles de aves en torno al recurso savia. Para M. cactorum y las especies de aves que consumieron savia, el consumo de savia fue marcadamente estacional, posiblemente asociado a periodos de escasez de recursos. Melanerpes cactorum defendió activamente las perforaciones ante algunas especies de aves cuya masa corporal fue menor a la de los carpinteros. Las especies nectarívoras especialistas y facultativas con alta tasa de asimilación de sacarosa representaron una importante proporción de las aves que consumieron savia. En el sistema carpinteros–savia–aves consumidoras de savia, el consumo de este recurso depende de características fisiológicas y comportamentales de las especies, como así también de la disponibilidad de otros recursos alimenticios en los ambientes que habitan.Fil: Nuñez Montellano, Maria Gabriela. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; ArgentinaFil: Blendinger, Pedro Gerardo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; ArgentinaFil: Macchi, Leandro. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; Argentin

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet