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Snape, J.

Publications and source records attributed to Snape, J..

5 recordsLinked to original sources

Common non-antibiotic drugs enhance selection for antimicrobial resistance in mixture with ciprofloxacin

Antimicrobial resistance (AMR) is a major health concern, and a range of antibiotic and non-antibiotic agents can select for AMR across a range of concentrations. Selection for AMR is often investigated using single compounds, however, in the natural environment and the human body, pharmaceuticals will be present as mixtures, including both non-antibiotic drugs (NADs), and antibiotics. Here, we assessed the effects of one of three NADs in combination with ciprofloxacin, a commonly used antibiotic that is often found at concentrations in global freshwaters sufficiently high to select for AMR. We used a combination of growth assays and qPCR to determine selective concentrations of mixtures and used metagenome sequencing to identify changes to the resistome and community composition. The selective concentration of ciprofloxacin was reduced from 40{micro}g/L to 10{micro}g/L in the mixtures, and mixtures showed a stronger selection for some AMR genes such as tolC and qnrB. The communities exposed to the mixtures also showed changed community compositions. These results demonstrate that NADs and ciprofloxacin are more selective than ciprofloxacin alone, and these mixtures can cause distinct changes to the community composition. This indicates that future work should consider combinations of antibiotics and NADs as drivers of AMR when considering its maintenance and acquisition.

microbiology↗

Antimicrobial effects, and selection for AMR by non-antibiotic drugs on bacterial communities

Antimicrobial resistance (AMR) is a major threat to human, veterinary, and agricultural health. AMR can be directly selected for by antibiotics, and indirectly co-selected for by biocides and metals. Some evidence suggests that non-antibiotic drugs (NADs) can co-select for AMR, but previous work focused on exposing single model bacterial species to predominately high concentrations of NADs. Here, we determined the antimicrobial effect and selective potential of three commonly used NADs against a complex bacterial community using a combination of culture based, metagenomic, and metratranscriptomic approaches. We found that three of five NADs tested on growth significantly reduced growth of a bacterial community, although only one (17-{beta}-estradiol) selected for an AMR marker using qPCR. Whole metagenome sequencing indicated that there was no clear strong selection by NADs for antibiotic resistance genes, nor effects on community composition. However, some changes in relative abundance of metal resistance genes were observed after exposure to diclofenac, metformin, and 17-{beta}-estradiol. Together, these results indicate that the NADs tested likely do not strongly select for AMR at both clinically and environmentally relevant concentrations.

microbiology↗

Natural selection towards wild-type in composite cross populations of winter wheat

Most of our crops are grown in monoculture with single genotypes grown over wide acreage. An alternative approach, where segregating populations are used as crops is an exciting possibility, but outcomes of natural selection upon this type of crop are not well understood. We tracked allelic frequency changes in evolving composite cross populations (CCPs) of wheat grown over ten generations under organic and conventional farming. At three generations, each population was genotyped with 19 SSR and 8 SNP markers. The latter were diagnostic for major functional genes. Gene diversity was constant at SSR markers but decreased over time for genic markers. Population differentiation between the four locations could not be detected, suggesting that organic vs. non-organic crop management did not drive allele frequency changes. However, we did see changes for genes controlling plant height and phenology in all populations independently and consistently. We interpret these changes as the result of a consistent natural selection towards wild-type. Independent selection for alleles that are associated with plant height suggests that competition for light was central, resulting in the predominance of stronger intraspecific competitors, and highlighting a potential trade-off between individual and population performance.

genetics↗

NOVEL INSIGHTS INTO SELECTION FOR ANTIBIOTIC RESISTANCE IN COMPLEX MICROBIAL COMMUNITIES

Recent research has demonstrated 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 the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low sub-inhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a two 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 on 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.

microbiology↗

Increased pericarp cell length underlies a major QTL for grain weight in hexaploid wheat

O_LICrop yields must increase to address food insecurity. Grain weight, determined by grain length and width, is an important yield component, but our understanding of the underlying genes and mechanisms is limited.\nC_LIO_LIWe used genetic mapping and near isogenic lines (NILs) to identify, validate and fine map a major quantitative trait loci (QTL) on wheat chromosome 5A associated with grain weight. Detailed phenotypic characterisation of developing and mature grains from the NILs was performed.\nC_LIO_LIWe identified a stable and robust QTL associated with a 6.9 % increase in grain weight. The positive interval leads to 4.0 % longer grains, with differences first visible twelve days post fertilization. This grain length effect was fine-mapped to a 4.3 cM interval. The locus also has a pleiotropic effect on grain width (1.5 %) during late grain development that determines the relative magnitude of the grain weight increase. Positive NILs have increased maternal pericarp cell length, an effect which is independent of absolute grain length.\nC_LIO_LIThese results provide direct genetic evidence that pericarp cell length affects final grain size and weight in polyploid wheat. We propose that combining genes which control distinct biological mechanisms, such as cell expansion and proliferation, will enhance crop yields.\nC_LI

plant biology↗