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  1. Article ; Online: Null models for gene enrichment in plasmids.

    Shaw, Liam P

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 21

    MeSH term(s) Plasmids/genetics ; Probability
    Language English
    Publishing date 2021-05-11
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2103665118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Visualizing and quantifying structural diversity around mobile resistance genes.

    Shaw, Liam P / Neher, Richard A

    Microbial genomics

    2023  Volume 9, Issue 12

    Abstract: Understanding the evolution of mobile genes is important for understanding the spread of antimicrobial resistance (AMR). Many clinically important AMR genes have been mobilized by mobile genetic elements (MGEs) on the kilobase scale, such as integrons ... ...

    Abstract Understanding the evolution of mobile genes is important for understanding the spread of antimicrobial resistance (AMR). Many clinically important AMR genes have been mobilized by mobile genetic elements (MGEs) on the kilobase scale, such as integrons and transposons, which can integrate into both chromosomes and plasmids and lead to rapid spread of the gene through bacterial populations. Looking at the flanking regions of these mobile genes in diverse genomes can highlight common structures and reveal patterns of MGE spread. However, historically this has been a largely descriptive process, relying on gene annotation and expert knowledge. Here we describe a general method to visualize and quantify the structural diversity around genes using pangraph to find blocks of homologous sequence. We apply this method to a set of 12 clinically important beta-lactamase genes and provide interactive visualizations of their flanking regions at https://liampshaw.github.io/flanking-regions. We show that nucleotide-level variation in the mobile gene itself generally correlates with increased structural diversity in its flanking regions, demonstrating a relationship between rates of mutational evolution and rates of structural evolution, and find a bias for greater structural diversity upstream. Our framework is a starting point to investigate general rules that apply to the horizontal spread of new genes through bacterial populations.
    MeSH term(s) Plasmids/genetics ; Bacteria/genetics ; beta-Lactamases/genetics ; Integrons
    Chemical Substances beta-Lactamases (EC 3.5.2.6)
    Language English
    Publishing date 2023-12-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.001168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: PanGraph

    Noll, Nicholas / Molari, Marco / Shaw, Liam P / Neher, Richard A

    Microbial genomics

    2023  Volume 9, Issue 6

    Abstract: The genomic diversity of microbes is commonly parameterized as SNPs relative to a reference genome of a well-characterized, but arbitrary, isolate. However, any reference genome contains only a fraction of the ... ...

    Abstract The genomic diversity of microbes is commonly parameterized as SNPs relative to a reference genome of a well-characterized, but arbitrary, isolate. However, any reference genome contains only a fraction of the microbial
    MeSH term(s) Genomics ; Genome, Bacterial
    Language English
    Publishing date 2023-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2835258-0
    ISSN 2057-5858 ; 2057-5858
    ISSN (online) 2057-5858
    ISSN 2057-5858
    DOI 10.1099/mgen.0.001034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Restriction-modification systems have shaped the evolution and distribution of plasmids across bacteria.

    Shaw, Liam P / Rocha, Eduardo P C / MacLean, R Craig

    Nucleic acids research

    2023  Volume 51, Issue 13, Page(s) 6806–6818

    Abstract: Many novel traits such as antibiotic resistance are spread by plasmids between species. Yet plasmids have different host ranges. Restriction-modification systems (R-M systems) are by far the most abundant bacterial defense system and therefore represent ... ...

    Abstract Many novel traits such as antibiotic resistance are spread by plasmids between species. Yet plasmids have different host ranges. Restriction-modification systems (R-M systems) are by far the most abundant bacterial defense system and therefore represent one of the key barriers to plasmid spread. However, their effect on plasmid evolution and host range has been neglected. Here we analyse the avoidance of targets of the most abundant R-M systems (Type II) for complete genomes and plasmids across bacterial diversity. For the most common target length (6 bp) we show that target avoidance is strongly correlated with the taxonomic distribution of R-M systems and is greater in plasmid genes than core genes. We find stronger avoidance of R-M targets in plasmids which are smaller and have a broader host range. Our results suggest two different evolutionary strategies for plasmids: small plasmids primarily adapt to R-M systems by tuning their sequence composition, and large plasmids primarily adapt through the carriage of additional genes protecting from restriction. Our work provides systematic evidence that R-M systems are important barriers to plasmid transfer and have left their mark on plasmids over long evolutionary time.
    MeSH term(s) DNA Restriction-Modification Enzymes/genetics ; Plasmids/genetics ; Bacteria/genetics ; Adaptation, Physiological ; Drug Resistance, Microbial
    Chemical Substances DNA Restriction-Modification Enzymes
    Language English
    Publishing date 2023-05-31
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad452
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The oral microbiome.

    Shaw, Liam P / Smith, Andrew M / Roberts, Adam P

    Emerging topics in life sciences

    2021  Volume 1, Issue 4, Page(s) 287–296

    Abstract: The human microbiome is receiving a great deal of attention as its role in health and disease becomes ever more apparent. The oral microbiome, perhaps due to the ease with which we can obtain samples, is arguably the most well-studied human microbiome to ...

    Abstract The human microbiome is receiving a great deal of attention as its role in health and disease becomes ever more apparent. The oral microbiome, perhaps due to the ease with which we can obtain samples, is arguably the most well-studied human microbiome to date. It is obvious, however, that we have only just begun to scratch the surface of the complex bacterial and bacterial-host interactions within this complex community. Here, we describe the factors which are known to influence the development of the seemingly globally conserved, core, oral microbiome and those which are likely to be responsible for the observed differences at the individual level. We discuss the paradoxical situation of maintaining a stable core microbiome which is at the same time incredibly resilient and adaptable to many different stresses encountered in the open environment of the oral cavity. Finally, we explore the interactions of the oral microbiome with the host and discuss the interactions underlying human health and disease.
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2882721-1
    ISSN 2397-8554 ; 2397-8554 ; 2397-8562
    ISSN (online) 2397-8554
    ISSN 2397-8554 ; 2397-8562
    DOI 10.1042/ETLS20170040
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  6. Article: Portable sequencing, genomic data, and scale in global emerging infectious disease surveillance.

    Shaw, Liam P / Sugden, Nicola C

    Geo : geography and environment

    2018  Volume 5, Issue 2, Page(s) e00066

    Abstract: Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not ... ...

    Abstract Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not been integrated into real-time responses, but portable DNA sequencing technology has prompted optimism among epidemiologists. Specifically, attention has focused on the goal of a "sequencing singularity": the integration of portable sequencers in a worldwide event-based surveillance network with other digital data (Gardy & Loman,
    Keywords covid19
    Language English
    Publishing date 2018-12-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2778711-4
    ISSN 2054-4049
    ISSN 2054-4049
    DOI 10.1002/geo2.66
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings.

    Ogunlana, Lois / Kaur, Divjot / Shaw, Liam P / Jangir, Pramod / Walsh, Timothy / Uphoff, Stephan / MacLean, R C

    The ISME journal

    2023  Volume 17, Issue 11, Page(s) 2058–2069

    Abstract: Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene ...

    Abstract Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene that confers resistance to colistin, an agricultural antibiotic that is used as a last resort for the treatment of multi-drug resistant infections. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E. coli to reduce the fitness cost of mcr-1 while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low-cost/high-resistance mcr-1 alleles across an incredible diversity of E. coli strains, further stabilising mcr-1 at the species level. Regulatory mutations were associated with increased mcr-1 stability in pig farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how regulatory evolution and plasmid transfer can combine to stabilise resistance and limit the impact of reducing antibiotic consumption.
    MeSH term(s) Animals ; Swine ; Colistin/pharmacology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Drug Resistance, Bacterial/genetics ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Plasmids/genetics ; Microbial Sensitivity Tests
    Chemical Substances Colistin (Z67X93HJG1) ; Escherichia coli Proteins ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-09-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2406536-5
    ISSN 1751-7370 ; 1751-7362
    ISSN (online) 1751-7370
    ISSN 1751-7362
    DOI 10.1038/s41396-023-01509-7
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  8. Article ; Online: Portable sequencing, genomic data, and scale in global emerging infectious disease surveillance

    Shaw, Liam P. / Sugden, Nicola C.

    Geo

    Abstract: Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not ... ...

    Abstract Emerging infectious diseases (EIDs) occur when pathogens unpredictably spread into new contexts. EID surveillance systems seek to rapidly identify EID outbreaks to contain spread and improve public health outcomes. Sequencing data has historically not been integrated into real‐time responses, but portable DNA sequencing technology has prompted optimism among epidemiologists. Specifically, attention has focused on the goal of a “sequencing singularity”: the integration of portable sequencers in a worldwide event‐based surveillance network with other digital data (Gardy & Loman, Nature Reviews Genetics, 19, 2018, p. 9). The sequencing singularity vision is a powerful socio‐technical imaginary, shaping the discourse around the future of portable sequencing. Ethical and practical issues are bound by the vision in two ways: they are framed only as obstacles, and they are formulated only at the scales made visible by its implicit geography. This geography privileges two extremes of scale – the genomic and the global – and leaves intermediate scales comparatively unmapped. We explore how widespread portable sequencing could challenge this geography. Portable sequencers put the ability to produce genomic data in the hands of the individual. The explicit assertion of rights over data may therefore become a matter disputed more at an interpersonal scale than an international one. Portable sequencers also promise ubiquitous, indiscriminate sequencing of the total metagenomic content of samples, raising the question of what (or who) is under surveillance and inviting consideration of the human microbiome and more‐than‐human geographies. We call into question a conception of a globally integrated stream of sequencing data as composed mostly of “noise,” within which signals of pathogen “emergence” are “hidden,” considering it instead from the perspective of recent work into more‐than‐human geographies. Our work highlights a practical need for researchers to consider both the alternative possibilities they foreclose as well as the exciting opportunities they move towards when they deploy their visions of the future.
    Keywords covid19
    Publisher PMC
    Document type Article ; Online
    DOI 10.1002/geo2.66
    Database COVID19

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  9. Article ; Online: Pre-existing chromosomal polymorphisms in pathogenic

    Jangir, Pramod K / Yang, Qiue / Shaw, Liam P / Caballero, Julio Diaz / Ogunlana, Lois / Wheatley, Rachel / Walsh, Timothy / MacLean, R Craig

    eLife

    2022  Volume 11

    Abstract: Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a 'last ...

    Abstract Bacterial pathogens show high levels of chromosomal genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance by plasmid acquisition remains unclear. Here, we address this problem in the context of colistin, a 'last line of defence' antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Colistin/pharmacology ; Drug Resistance, Bacterial/genetics ; Escherichia coli/genetics ; Escherichia coli Proteins/genetics ; Microbial Sensitivity Tests ; Plasmids/genetics
    Chemical Substances Anti-Bacterial Agents ; Escherichia coli Proteins ; MCR-1 protein, E coli ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2022-08-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.78834
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  10. Article: A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.

    Smith, Richard P / May, Hannah E / AbuOun, Manal / Stubberfield, Emma / Gilson, Daniel / Chau, Kevin K / Crook, Derrick W / Shaw, Liam P / Read, Daniel S / Stoesser, Nicole / Vilar, Maria Jose / Anjum, Muna F

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1070340

    Abstract: Introduction: There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, ... ...

    Abstract Introduction: There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.
    Methods: A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.
    Results: Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.
    Discussion: The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.
    Language English
    Publishing date 2023-03-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1070340
    Database MEDical Literature Analysis and Retrieval System OnLINE

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