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Article ; Online: Portable sequencing, genomic data, and scale in global emerging infectious disease surveillance

Liam P. Shaw / Nicola C. Sugden

Geo: Geography and Environment, Vol 5, Iss 2, Pp n/a-n/a (2018)

2018

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 ...
Keywords	emerging infectious disease surveillance ; global health ; human microbiome ; more‐than‐human geography ; portable sequencing ; Environmental sciences ; GE1-350 ; Geography (General) ; G1-922
Subject code	910
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence

Pramod K Jangir / Lois Ogunlana / Petra Szili / Marton Czikkely / Liam P Shaw / Emily J Stevens / Yang Yu / Qiue Yang / Yang Wang / Csaba Pál / Timothy R Walsh / Craig R MacLean

eLife, Vol

2023 Volume 12

Abstract: Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a ... ...

Abstract	Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.
Keywords	pathogen evolution ; mobile colistin resistance ; antimicrobial resistance ; antimicrobial peptides ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enterobacterales plasmid sharing amongst human bloodstream infections, livestock, wastewater, and waterway niches in Oxfordshire, UK

William Matlock / Samuel Lipworth / Kevin K Chau / Manal AbuOun / Leanne Barker / James Kavanagh / Monique Andersson / Sarah Oakley / Marcus Morgan / Derrick W Crook / Daniel S Read / Muna Anjum / Liam P Shaw / Nicole Stoesser / REHAB Consortium

eLife, Vol

2023 Volume 12

Abstract: Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, the extent of plasmid sharing and evolution between Enterobacterales causing human infections ...

Abstract	Plasmids enable the dissemination of antimicrobial resistance (AMR) in common Enterobacterales pathogens, representing a major public health challenge. However, the extent of plasmid sharing and evolution between Enterobacterales causing human infections and other niches remains unclear, including the emergence of resistance plasmids. Dense, unselected sampling is essential to developing our understanding of plasmid epidemiology and designing appropriate interventions to limit the emergence and dissemination of plasmid-associated AMR. We established a geographically and temporally restricted collection of human bloodstream infection (BSI)-associated, livestock-associated (cattle, pig, poultry, and sheep faeces, farm soils) and wastewater treatment work (WwTW)-associated (influent, effluent, waterways upstream/downstream of effluent outlets) Enterobacterales. Isolates were collected between 2008 and 2020 from sites <60 km apart in Oxfordshire, UK. Pangenome analysis of plasmid clusters revealed shared ‘backbones’, with phylogenies suggesting an intertwined ecology where well-conserved plasmid backbones carry diverse accessory functions, including AMR genes. Many plasmid ‘backbones’ were seen across species and niches, raising the possibility that plasmid movement between these followed by rapid accessory gene change could be relatively common. Overall, the signature of identical plasmid sharing is likely to be a highly transient one, implying that plasmid movement might be occurring at greater rates than previously estimated, raising a challenge for future genomic One Health studies.
Keywords	plasmid ; Enterobacterales ; antimicrobial resistance ; bloodstream infections ; One Health ; genomic epidemiology ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla NDM

Mislav Acman / Ruobing Wang / Lucy van Dorp / Liam P. Shaw / Qi Wang / Nina Luhmann / Yuyao Yin / Shijun Sun / Hongbin Chen / Hui Wang / Francois Balloux

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 13

Abstract: Gene bla NDM, conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al. study the dynamics underlying bla NDM dissemination across over 6000 bacterial genomes, and ... ...

Abstract	Gene bla NDM, conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al. study the dynamics underlying bla NDM dissemination across over 6000 bacterial genomes, and identify mobile genetic elements and specific mobilisation events likely involved in the gene’s global spread.
Keywords	Science ; Q
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of resistance to a last-resort antibiotic

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

eLife, Vol

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 Escherichia coli to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistance between the chromosomal mutations and a mobile resistance gene. Analysis of public genomic datasets shows that lpxC polymorphisms are common in pathogenic E. coli, including those carrying MCR-1, highlighting the clinical relevance of this interaction. Importantly, lpxC diversity is high in pathogenic E. coli from regions with no history of MCR-1 acquisition, suggesting that pre-existing lpxC polymorphisms potentiated the evolution of high-level colistin resistance by MCR-1 acquisition. More broadly, these findings highlight the importance of standing genetic variation and plasmid/chromosomal interactions in the evolutionary dynamics of antibiotic resistance.
Keywords	antibiotic resistance evolution ; pathogen evolution ; epistasis ; plasmids ; colistin ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2

Lucy van Dorp / Damien Richard / Cedric C. S. Tan / Liam P. Shaw / Mislav Acman / François Balloux

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 8

Abstract: SARS-CoV-2 has emerged recently and may still adapt to the human host. Here the authors show that none of the so far identified recurrent mutations in SARS-CoV-2 are significantly associated with increased viral transmission. ...

Abstract	SARS-CoV-2 has emerged recently and may still adapt to the human host. Here the authors show that none of the so far identified recurrent mutations in SARS-CoV-2 are significantly associated with increased viral transmission.
Keywords	Science ; Q
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Electronic application to improve management of infections in low-income neonatal units

Michelle Heys / Caroline Crehan / Nigel Klein / Mario Cortina Borja / Samuel R Neal / Hannah Gannon / Simbarashe Chimhuya / Gwendoline Chimhini / Liam P Shaw / Tim Hull-Bailey / Rashida A Ferrand / Valerie Robertson / Felicity C Fitzgerald

BMJ Open Quality, Vol 10, Iss

pilot implementation of the NeoTree beta app in a public sector hospital in Zimbabwe

2021 Volume 1

Abstract: There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of ... ...

Abstract	There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing handwritten clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central Hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings and to improve turnaround time for blood culture results among other quality improvement indicators. There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.
Keywords	Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients

Julio Diaz Caballero / Rachel M. Wheatley / Natalia Kapel / Carla López-Causapé / Thomas Van der Schalk / Angus Quinn / Liam P. Shaw / Lois Ogunlana / Claudia Recanatini / Basil Britto Xavier / Leen Timbermont / Jan Kluytmans / Alexey Ruzin / Mark Esser / Surbhi Malhotra-Kumar / Antonio Oliver / R. Craig MacLean

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 12

Abstract: Abstract Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de ...

Abstract	Abstract Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.
Keywords	Science ; Q
Subject code	630
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China

Hongbin Chen / Yuyao Yin / Lucy van Dorp / Liam P. Shaw / Hua Gao / Mislav Acman / Jizhen Yuan / Fengning Chen / Shijun Sun / Xiaojuan Wang / Shuguang Li / Yawei Zhang / Rhys A. Farrer / Hui Wang / Francois Balloux

Genome Medicine, Vol 13, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. ... ...

Abstract	Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear. Methods Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes. Results ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 ...
Keywords	Methicillin-resistant Staphylococcus aureus (MRSA) ; Molecular evolution ; Lineage replacement ; Phylogeny ; Phylogeography ; Virulence ; Medicine ; R ; Genetics ; QH426-470
Subject code	580
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient

Rachel M. Wheatley / Julio Diaz Caballero / Thomas E. van der Schalk / Fien H. R. De Winter / Liam P. Shaw / Natalia Kapel / Claudia Recanatini / Leen Timbermont / Jan Kluytmans / Mark Esser / Alicia Lacoma / Cristina Prat-Aymerich / Antonio Oliver / Samir Kumar-Singh / Surbhi Malhotra-Kumar / R. Craig MacLean

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 11

Abstract: In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs. ...

Abstract	In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs.
Keywords	Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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