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22 results on '"Rowe, Will P. M."'

1. Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Author

Pulford, Caisey V., Perez-Sepulveda, Blanca M., Canals, Rocío, Bevington, Jessica A., Bengtsson, Rebecca J., Wenner, Nicolas, Rodwell, Ella V., Kumwenda, Benjamin, Zhu, Xiaojun, Bennett, Rebecca J., Stenhouse, George E., Malaka De Silva, P., Webster, Hermione J., Bengoechea, Jose A., Dumigan, Amy, Tran-Dien, Alicia, Prakash, Reenesh, Banda, Happy C., Alufandika, Lovemore, Mautanga, Mike P., Bowers-Barnard, Arthur, Beliavskaia, Alexandra Y., Predeus, Alexander V., Rowe, Will P. M., Darby, Alistair C., Hall, Neil, Weill, François-Xavier, Gordon, Melita A., Feasey, Nicholas A., Baker, Kate S., and Hinton, Jay C. D.

Published
2021
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2. Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences

Author

Carrieri, Anna Paola, Haiminen, Niina, Maudsley-Barton, Sean, Gardiner, Laura-Jayne, Murphy, Barry, Mayes, Andrew E., Paterson, Sarah, Grimshaw, Sally, Winn, Martyn, Shand, Cameron, Hadjidoukas, Panagiotis, Rowe, Will P. M., Hawkins, Stacy, MacGuire-Flanagan, Ashley, Tazzioli, Jane, Kenny, John G., Parida, Laxmi, Hoptroff, Michael, and Pyzer-Knapp, Edward O.

Published
2021
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4. Succinate utilisation by Salmonella is inhibited by multiple regulatory systems.

Author

Wenner, Nicolas, Zhu, Xiaojun, Rowe, Will P. M., Händler, Kristian, and Hinton, Jay C. D.

Subjects
SALMONELLA, SALMONELLA enterica serovar typhimurium, OPERONS, SALMONELLA enterica, SALMONELLA diseases, RNA-binding proteins, ENTEROBACTERIACEAE, PATHOGENIC bacteria
Abstract

Succinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these infection niches are colonised by the pathogenic bacterium Salmonella enterica serovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source for in vitro cultivation, Salmonella and other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we use an experimental evolution approach to isolate fast-growing mutants during growth of S. Typhimurium on succinate containing minimal medium. Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation. Our discoveries shed light on the redundant regulatory systems that tightly regulate the utilisation of succinate. We speculate that the control of central carbon metabolism by multiple regulatory systems in Salmonella governs the infection niche-specific utilisation of succinate. Author summary: During infection, Salmonella enterica serovar Typhimurium must efficiently utilise the nutrients provided by the host and the microbiota. Within host niches colonised by Salmonella, key carbon source is succinate, which is abundant in both the gut and within macrophages. Although S. Typhimurium possesses all the molecular machinery to import and catabolise succinate, the utilisation of this carbon source is strongly inhibited under laboratory conditions. Here, we have used diverse genetic approaches to discover that several distinct genetic regulatory systems act in concert to repress succinate utilisation by Salmonella. Our study sheds new light on how carbon source utilisation is managed by this important model enteropathogenic bacterium. [ABSTRACT FROM AUTHOR]

Published
2024
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7. CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., Loman, Nicholas J., The COVID-19 Genomics UK (COG-UK) Consortium, Bashton, Matthew, Smith, Darren, Nelson, Andrew, Young, Greg, McCann, Clare, Harrison, Ewan [0000-0003-2720-0507], Peacock, Sharon [0000-0002-1718-2782], and Apollo - University of Cambridge Repository

Subjects
QH301-705.5, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Genomics, Genome, Viral, Biology, QH426-470, Genome, User-Computer Interface, Pandemic, Genetics, Humans, Biology (General), Whole genome sequencing, Whole Genome Sequencing, SARS-CoV-2, C100, fungi, COVID-19, C500, Sequence Analysis, DNA, Cloud Computing, Data science, C900, United Kingdom, Metadata, B900, Editorial, Software deployment, Epidemiological Monitoring
Abstract

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-021-02395-y.

Published
2021
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8. Additional file 1 of CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., and Loman, Nicholas J.

Abstract

Additional file 1. The COVID-19 Genomics UK (COG-UK) Consortium.

Published
2021
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9. Additional file 2 of CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Author

Nicholls, Samuel M., Poplawski, Radoslaw, Bull, Matthew J., Underwood, Anthony, Chapman, Michael, Abu-Dahab, Khalil, Taylor, Ben, Colquhoun, Rachel M., Rowe, Will P. M., Jackson, Ben, Hill, Verity, O’Toole, Áine, Rey, Sara, Southgate, Joel, Amato, Roberto, Livett, Rich, Gonçalves, Sónia, Harrison, Ewan M., Peacock, Sharon J., Aanensen, David M., Rambaut, Andrew, Connor, Thomas R., and Loman, Nicholas J.

Abstract

Additional file 2: Table 3. COG-UK full metadata standard.

Published
2021
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10. Genome-Wide Identification and Expression Analysis of SOS Response Genes in Salmonella enterica Serovar Typhimurium

Author

Universidad de Sevilla. Departamento de Genética, Mérida Floriano, Ángela, Rowe, Will P. M., Casadesús Pursals, Josep, Universidad de Sevilla. Departamento de Genética, Mérida Floriano, Ángela, Rowe, Will P. M., and Casadesús Pursals, Josep

Abstract

A bioinformatic search for LexA boxes, combined with transcriptomic detection of loci responsive to DNA damage, identified 48 members of the SOS regulon in the genome of Salmonella enterica serovar Typhimurium. Single cell analysis using fluorescent fusions revealed that heterogeneous expression is a common trait of SOS response genes, with formation of SOSOFF and SOSON subpopulations. Phenotypic cell variants formed in the absence of external DNA damage show gene expression patterns that are mainly determined by the position and the heterology index of the LexA box. SOS induction upon DNA damage produces SOSOFF and SOSON subpopulations that contain live and dead cells. The nature and concentration of the DNA damaging agent and the time of exposure are major factors that influence the population structure upon SOS induction. An analogy can thus be drawn between the SOS response and other bacterial stress responses that produce phenotypic cell variants.

Published
2021

12. Stepwise evolution of Salmonella Typhimurium ST313 causing bloodstream infection in Africa

Author

Pulford, Caisey V., primary, Perez-Sepulveda, Blanca M., additional, Canals, Rocío, additional, Bevington, Jessica A., additional, Bengtsson, Rebecca J., additional, Wenner, Nicolas, additional, Rodwell, Ella V., additional, Kumwenda, Benjamin, additional, Zhu, Xiaojun, additional, Bennett, Rebecca J., additional, Stenhouse, George E., additional, Malaka De Silva, P., additional, Webster, Hermione J., additional, Bengoechea, Jose A., additional, Dumigan, Amy, additional, Tran-Dien, Alicia, additional, Prakash, Reenesh, additional, Banda, Happy C., additional, Alufandika, Lovemore, additional, Mautanga, Mike P., additional, Bowers-Barnard, Arthur, additional, Beliavskaia, Alexandra Y., additional, Predeus, Alexander V., additional, Rowe, Will P. M., additional, Darby, Alistair C., additional, Hall, Neil, additional, Weill, François-Xavier, additional, Gordon, Melita A., additional, Feasey, Nicholas A., additional, Baker, Kate S., additional, and Hinton, Jay C. D., additional

Published
2020
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13. Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580

Author

Canals, Rocio, Larsson, Disa, Kroger, Carsten, Owen, Sian V., Fong, Wai Yee, Lacharme-Lora, Lizeth, Zhu, Xiaojun, Wenner, Nicolas, Carden, Sarah E., Honeycutt, Jared, Monack, Denise M., Kingsley, Robert A., Brownridge, Philip, Chaudhuri, Roy R., Rowe, Will P. M., Predeus, Alexander V., Hokamp, Karsten, Gordon, Melita A., Hinton, Jay C. D., Canals, Rocio, Larsson, Disa, Kroger, Carsten, Owen, Sian V., Fong, Wai Yee, Lacharme-Lora, Lizeth, Zhu, Xiaojun, Wenner, Nicolas, Carden, Sarah E., Honeycutt, Jared, Monack, Denise M., Kingsley, Robert A., Brownridge, Philip, Chaudhuri, Roy R., Rowe, Will P. M., Predeus, Alexander V., Hokamp, Karsten, Gordon, Melita A., and Hinton, Jay C. D.

Abstract

Salmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in 16 infection-relevant growth conditions. Comparison of transcriptional patterns identified virulence and metabolic genes that were differentially expressed between D23580 versus 4/74, many of which were validated by proteomics. We also uncovered the S. Typhimurium D23580 and 4/74 genes that showed expression differences during infection of murine macrophages. Our comparative transcriptomic data are presented in a new enhanced version of the Salmonella expression compendium, SalComD23580: http://bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl. We discovered that the ablation of melibiose utilization was caused by three independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolize this carbon source has been negatively selected during ST313 evolution. The data revealed a novel, to our knowledge, plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multicondition analyses to pinpoint key phenotypic differences between bacterial pathovariants.

Published
2019
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14. Overexpression of antibiotic resistance genes in hospital effluents over time

Author

Rowe, Will P. M., Baker-Austin, Craig, Verner-Jeffreys, David W., Ryan, Jim J., Micallef, Christianne, Maskell, Duncan J., Pearce, Gareth P., Maskell, Duncan [0000-0002-5065-653X], Pearce, Gareth [0000-0002-0656-6553], and Apollo - University of Cambridge Repository

Subjects
Farms, Gene Expression, Wastewater, dna, complex mixtures, beta-Lactam Resistance, antibiotics, resistance, Spatio-Temporal Analysis, Rivers, antibiotic, Humans, bacterial, rna, lactams, genes, Original Research, metagenomics, Bacteria, resistance genes, Gene Expression Profiling, Drug Resistance, Microbial, Anti-Bacterial Agents, Dairying, Genes, Bacterial, municipal, Water Microbiology, hospitals, protein, overexpression
Abstract

$\textbf{Objectives}$: Effluents contain a diverse abundance of antibiotic resistance genes that augment the resistome of receiving aquatic environments. However, uncertainty remains regarding their temporal persistence, transcription and response to anthropogenic factors, such as antibiotic usage. We present a spatiotemporal study within a river catchment (River Cam, UK) that aims to determine the contribution of antibiotic resistance gene-containing effluents originating from sites of varying antibiotic usage to the receiving environment. $\textbf{Methods}$: Gene abundance in effluents (municipal hospital and dairy farm) was compared against background samples of the receiving aquatic environment (i.e. the catchment source) to determine the resistome contribution of effluents. We used metagenomics and metatranscriptomics to correlate DNA and RNA abundance and identified differentially regulated gene transcripts. $\textbf{Results}$: We found that mean antibiotic resistance gene and transcript abundances were correlated for both hospital (ρ=0.9, two-tailed $\textit{P}$

Published
2017

15. Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580

Author

Canals, Rocío, primary, Hammarlöf, Disa L., additional, Kröger, Carsten, additional, Owen, Siân V., additional, Fong, Wai Yee, additional, Lacharme-Lora, Lizeth, additional, Zhu, Xiaojun, additional, Wenner, Nicolas, additional, Carden, Sarah E., additional, Honeycutt, Jared, additional, Monack, Denise M., additional, Kingsley, Robert A., additional, Brownridge, Philip, additional, Chaudhuri, Roy R., additional, Rowe, Will P. M., additional, Predeus, Alexander V., additional, Hokamp, Karsten, additional, Gordon, Melita A., additional, and Hinton, Jay C. D., additional

Published
2019
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16. Adding function to the genome of AfricanSalmonellaST313

Author

Canals, Rocío, primary, Hammarlöf, Disa L., additional, Kröger, Carsten, additional, Owen, Siân V., additional, Fong, Wai Yee, additional, Lacharme-Lora, Lizeth, additional, Zhu, Xiaojun, additional, Wenner, Nicolas, additional, Carden, Sarah E., additional, Honeycutt, Jared, additional, Monack, Denise M., additional, Kingsley, Robert A., additional, Brownridge, Philip, additional, Chaudhuri, Roy R., additional, Rowe, Will P. M., additional, Predeus, Alexander V., additional, Hokamp, Karsten, additional, Gordon, Melita A., additional, and Hinton, Jay C. D., additional

Published
2018
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17. Streaming histogram sketching for rapid microbiome analytics

Author

Rowe, Will P. M., primary, Carrieri, Anna Paola, additional, Alcon-Giner, Cristina, additional, Caim, Shabhonam, additional, Shaw, Alex, additional, Sim, Kathleen, additional, Kroll, J Simon, additional, Hall, Lindsay J., additional, Pyzer-Knapp, Edward O., additional, and Winn, Martyn D., additional

Published
2018
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19. Public health surveillance in the UK revolutionises our understanding of the invasive Salmonella Typhimurium epidemic in Africa

Author

Ashton, Philip M., primary, Owen, Siân V., additional, Kaindama, Lukeki, additional, Rowe, Will P. M., additional, Lane, Chris R., additional, Larkin, Lesley, additional, Nair, Satheesh, additional, Jenkins, Claire, additional, de Pinna, Elizabeth M., additional, Feasey, Nicholas A., additional, Hinton, Jay C. D., additional, and Dallman, Timothy J., additional

Published
2017
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20. Salmonella enterica serovar Typhimurium ST313 responsible for gastroenteritis in the UK are genetically distinct from isolates causing bloodstream infections in Africa

Author

Ashton, Philip M., primary, Owen, Sian V., additional, Kaindama, Lukeki, additional, Rowe, Will P. M., additional, Lane, Chris, additional, Larkin, Lesley, additional, Nair, Satheesh, additional, Jenkins, Claire, additional, de Pinna, Elizabeth, additional, Feasey, Nicholas, additional, Hinton, Jay C. D., additional, and Dallman, Tim, additional

Published
2017
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22. CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

Author

Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, and Loman NJ

Subjects
COVID-19 epidemiology, Epidemiological Monitoring, Genome, Viral, Humans, Sequence Analysis, DNA, United Kingdom, User-Computer Interface, Whole Genome Sequencing, Cloud Computing, Genomics organization & administration, SARS-CoV-2 genetics
Abstract

In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.

Published
2021
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