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119 results on '"Wheeler, Nicole E."'

1. Applying data technologies to combat AMR: current status, challenges, and opportunities on the way forward

Author

Chindelevitch, Leonid, Jauneikaite, Elita, Wheeler, Nicole E., Allel, Kasim, Ansiri-Asafoakaa, Bede Yaw, Awuah, Wireko A., Bauer, Denis C., Beisken, Stephan, Fan, Kara, Grant, Gary, Graz, Michael, Khalaf, Yara, Liyanapathirana, Veranja, Montefusco-Pereira, Carlos, Mugisha, Lawrence, Naik, Atharv, Nanono, Sylvia, Nguyen, Anthony, Rawson, Timothy, Reddy, Kessendri, Ruzante, Juliana M., Schmider, Anneke, Stocker, Roman, Unruh, Leonhardt, Waruingi, Daniel, Graz, Heather, and van Dongen, Maarten

Subjects
Computer Science - Computers and Society, Computer Science - Artificial Intelligence, Computer Science - Machine Learning, Statistics - Applications, I.2.1, J.3
Abstract

Antimicrobial resistance (AMR) is a growing public health threat, estimated to cause over 10 million deaths per year and cost the global economy 100 trillion USD by 2050 under status quo projections. These losses would mainly result from an increase in the morbidity and mortality from treatment failure, AMR infections during medical procedures, and a loss of quality of life attributed to AMR. Numerous interventions have been proposed to control the development of AMR and mitigate the risks posed by its spread. This paper reviews key aspects of bacterial AMR management and control which make essential use of data technologies such as artificial intelligence, machine learning, and mathematical and statistical modelling, fields that have seen rapid developments in this century. Although data technologies have become an integral part of biomedical research, their impact on AMR management has remained modest. We outline the use of data technologies to combat AMR, detailing recent advancements in four complementary categories: surveillance, prevention, diagnosis, and treatment. We provide an overview on current AMR control approaches using data technologies within biomedical research, clinical practice, and in the "One Health" context. We discuss the potential impact and challenges wider implementation of data technologies is facing in high-income as well as in low- and middle-income countries, and recommend concrete actions needed to allow these technologies to be more readily integrated within the healthcare and public health sectors., Comment: 65 pages, 3 figures

Published
2022

4. Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group

Author

Baker, Kate S, Jauneikaite, Elita, Nunn, Jamie G, Midega, Janet T, Atun, Rifat, Holt, Kathryn E, Walia, Kamini, Howden, Benjamin P, Tate, Heather, Okeke, Iruka N, Carattoli, Alessandra, Hsu, Li Yang, Hopkins, Katie L, Muloi, Dishon M, Wheeler, Nicole E, Aanensen, David M, Mason, Lewis C E, Rodgus, Jonah, Hendriksen, Rene S, Essack, Sabiha Y, Egyir, Beverly, Halpin, Alison L, MacCannell, Duncan R, Campos, Josefina, Srikantiah, Padmini, Feasey, Nicholas A, and Peacock, Sharon J

Published
2023
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5. Progress and Prospects for a Nucleic Acid Screening Test Set.

Author

Wheeler, Nicole E., Bartling, Craig, Carter, Sarah R., Clore, Adam, Diggans, James, Flyangolts, Kevin, Gemler, Bryan T., Rife Magalis, Brittany, and Beal, Jacob

Abstract

Objective: DNA synthesis companies screen orders to detect controlled sequences with misuse risks. Assessing screening accuracy is challenging owing to the breadth of biological risks and ambiguities in risk definitions. Here, we detail an International Gene Synthesis Consortium working group's rationale and process to develop a prototype DNA synthesis screening test dataset, aiming to establish a baseline of screening system accuracy to compare with various screening approaches. Methodology: Construction of the prototype test dataset involved four tool developers screening nucleic acid sequences from three taxonomic clusters of controlled organisms (Orbivirus, Francisella tularensis, and Coccidioides). Results were mapped onto predefined, comparable categories, checking for consensus or conflicts. Conflicts were grouped based on gene annotation and resolved through discussion. Results: The process highlighted several long-standing challenges in DNA synthesis screening, including the qualitative differences in approaches taken by screening tools. Our findings highlight the lack of clarity in assessing pathogen sequences with respect to regulatory control language, compounded by scientific uncertainty. We illustrate the current degree of consensus and existing challenges using classification statistics and specific examples. Conclusions and Next Steps: This prototype underscores the necessity of expert-regulator coordination in assessing gene-associated risks, offering a template for creating test sets across all taxonomic groups on international control lists. Expanding the working group would enrich dataset comprehensiveness, enabling a transition from species-focused to function-focused regulatory controls. This sets the foundation for quality control, certification, and improved risk assessment in DNA synthesis screening. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Developing a Common Global Baseline for Nucleic Acid Synthesis Screening.

Author

Wheeler, Nicole E., Carter, Sarah R., Alexanian, Tessa, Isaac, Christopher, Yassif, Jaime, and Millet, Piers

Abstract

Introduction: Nucleic acid synthesis is a powerful tool that has revolutionized the life sciences. However, the misuse of synthetic nucleic acids could pose a serious threat to public health and safety. There is a need for international standards for nucleic acid synthesis screening to help prevent the misuse of this technology. Methods: We outline current barriers to the adoption of screening, which include the cost of developing screening tools and resources, adapting to existing commercial practices, internationalizing screening, and adapting screening to benchtop nucleic acid synthesis devices. To address these challenges, we then introduce the Common Mechanism for DNA Synthesis Screening, which was developed in consultation with a technical consortium of experts in DNA synthesis, synthetic biology, biosecurity, and policy, with the aim of addressing current barriers. The Common Mechanism software uses a variety of methods to identify sequences of concern, identify taxonomic best matches to regulated pathogens, and identify benign genes that can be cleared for synthesis. Finally, we describe outstanding challenges in the development of screening practices. Results: The Common Mechanism is a step toward ensuring the safe and responsible use of synthetic nucleic acids. It provides a baseline capability that overcomes challenges to nucleic acid synthesis screening and provides a solution for broader international adoption of screening practices. Conclusion: The Common Mechanism is a valuable tool for preventing the misuse of synthetic nucleic acids. It is a critical step toward ensuring the safe and responsible use of this powerful technology. [ABSTRACT FROM AUTHOR]

Published
2024
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9. An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation

Author

Van Puyvelde, Sandra, Pickard, Derek, Vandelannoote, Koen, Heinz, Eva, Barbé, Barbara, de Block, Tessa, Clare, Simon, Coomber, Eve L., Harcourt, Katherine, Sridhar, Sushmita, Lees, Emily A., Wheeler, Nicole E., Klemm, Elizabeth J., Kuijpers, Laura, Mbuyi Kalonji, Lisette, Phoba, Marie-France, Falay, Dadi, Ngbonda, Dauly, Lunguya, Octavie, Jacobs, Jan, Dougan, Gordon, and Deborggraeve, Stijn

Published
2019
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10. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Author

Lees, John A., Ferwerda, Bart, Kremer, Philip H. C., Wheeler, Nicole E., Serón, Mercedes Valls, Croucher, Nicholas J., Gladstone, Rebecca A., Bootsma, Hester J., Rots, Nynke Y., Wijmega-Monsuur, Alienke J., Sanders, Elisabeth A. M., Trzciński, Krzysztof, Wyllie, Anne L., Zwinderman, Aeilko H., van den Berg, Leonard H., van Rheenen, Wouter, Veldink, Jan H., Harboe, Zitta B., Lundbo, Lene F., de Groot, Lisette C. P. G. M., van Schoor, Natasja M., van der Velde, Nathalie, Ängquist, Lars H., Sørensen, Thorkild I. A., Nohr, Ellen A., Mentzer, Alexander J., Mills, Tara C., Knight, Julian C., du Plessis, Mignon, Nzenze, Susan, Weiser, Jeffrey N., Parkhill, Julian, Madhi, Shabir, Benfield, Thomas, von Gottberg, Anne, van der Ende, Arie, Brouwer, Matthijs C., Barrett, Jeffrey C., Bentley, Stephen D., and van de Beek, Diederik

Published
2019
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11. Beyond Biosecurity by Taxonomic Lists: Lessons, Challenges, and Opportunities.

Author

Millett, Piers, Alexanian, Tessa, Brink, Kathryn R., Carter, Sarah R., Diggans, James, Palmer, Megan J., Ritterson, Ryan, Sandbrink, Jonas B., and Wheeler, Nicole E.

Abstract

This article explores the challenges and limitations of using taxonomic lists in biosecurity regimes. While taxonomic lists are commonly used to regulate access to harmful organisms and toxins, they often lack specificity or clarity. Advances in biological engineering have further complicated the effectiveness of taxonomy-based control systems. The article suggests a more structured approach to designing biosecurity regimes, including understanding the goals of the regime, translating those goals into biological functions to be controlled, and identifying the most suitable tools for the job. It also proposes improvements to taxonomic lists, such as regular updates, inclusion of functional equivalence, consideration of ease of engineering, and clarification of language. Additionally, the article suggests alternative approaches, such as using reference databases and sequence-based methods, to better capture organisms that may pose harm. It emphasizes the need for improved sequence databases and the development of databases for known toxins and virulence factors. Ultimately, the article advocates for the development of more effective and tailored biosecurity tools. [Extracted from the article]

Published
2023
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22. Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Author

Argimón, Silvia, David, Sophia, Underwood, Anthony, Abrudan, Monica, Wheeler, Nicole E, Kekre, Mihir, Abudahab, Khalil, Yeats, Corin A, Goater, Richard, Taylor, Ben, Harste, Harry, Muddyman, Dawn, Feil, Edward J, Brisse, Sylvain, Holt, Kathryn, Donado-Godoy, Pilar, Ravikumar, KL, Okeke, Iruka N, Carlos, Celia, Aanensen, David M, NIHR Global Health Research Unit on Genomic Surveillance of Anti, and NIHR Global Health Research Unit on Genomic Surveillance

Abstract

BACKGROUND: Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. METHODS: We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16 537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1636 genomes from 4 low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. RESULTS: Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (eg, ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that 3 O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. CONCLUSIONS: Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national, and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance.

Published
2021

23. Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Author

Argimón, Silvia, primary, David, Sophia, additional, Underwood, Anthony, additional, Abrudan, Monica, additional, Wheeler, Nicole E., additional, Kekre, Mihir, additional, Abudahab, Khalil, additional, Yeats, Corin A., additional, Goater, Richard, additional, Taylor, Ben, additional, Harste, Harry, additional, Muddyman, Dawn, additional, Feil, Edward J., additional, Brisse, Sylvain, additional, Holt, Kathryn, additional, Donado-Godoy, Pilar, additional, Ravikumar, KL, additional, Okeke, Iruka N., additional, Carlos, Celia, additional, and Aanensen, David M., additional

Published
2021
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28. Increased antibiotic susceptibility inNeisseria gonorrhoeaethrough adaptation to the cervical environment

Author

Ma, Kevin C, primary, Mortimer, Tatum D, additional, Hicks, Allison L, additional, Wheeler, Nicole E, additional, Sánchez-Busó, Leonor, additional, Golparian, Daniel, additional, Taiaroa, George, additional, Rubin, Daniel HF, additional, Wang, Yi, additional, Williamson, Deborah A, additional, Unemo, Magnus, additional, Harris, Simon R, additional, and Grad, Yonatan H, additional

Published
2020
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29. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Author

Immuno/reuma onderzoek 7 (Montfrans), Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Immuno/reuma onderzoek 8 (Trzcinski), Projectafdeling ALS, ZL Neuromusculaire Ziekten Medisch, Brain, Regenerative Medicine and Stem Cells, Opleiding Neurologie, Lees, John A., Ferwerda, Bart, Kremer, Philip H.C., Wheeler, Nicole E., Serón, Mercedes Valls, Croucher, Nicholas J., Gladstone, Rebecca A., Bootsma, Hester J., Rots, Nynke Y., Wijmega-Monsuur, Alienke J., Sanders, Elisabeth A.M., Trzciński, Krzysztof, Wyllie, Anne L., Zwinderman, Aeilko H., van den Berg, Leonard H., van Rheenen, Wouter, Veldink, Jan H., Harboe, Zitta B., Lundbo, Lene F., de Groot, Lisette C.P.G.M., van Schoor, Natasja M., van der Velde, Nathalie, Ängquist, Lars H., Sørensen, Thorkild I.A., Nohr, Ellen A., Mentzer, Alexander J., Mills, Tara C., Knight, Julian C., du Plessis, Mignon, Nzenze, Susan, Weiser, Jeffrey N., Parkhill, Julian, Madhi, Shabir, Benfield, Thomas, von Gottberg, Anne, van der Ende, Arie, Brouwer, Matthijs C., Barrett, Jeffrey C., Bentley, Stephen D., van de Beek, Diederik, Immuno/reuma onderzoek 7 (Montfrans), Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Immuno/reuma onderzoek 8 (Trzcinski), Projectafdeling ALS, ZL Neuromusculaire Ziekten Medisch, Brain, Regenerative Medicine and Stem Cells, Opleiding Neurologie, Lees, John A., Ferwerda, Bart, Kremer, Philip H.C., Wheeler, Nicole E., Serón, Mercedes Valls, Croucher, Nicholas J., Gladstone, Rebecca A., Bootsma, Hester J., Rots, Nynke Y., Wijmega-Monsuur, Alienke J., Sanders, Elisabeth A.M., Trzciński, Krzysztof, Wyllie, Anne L., Zwinderman, Aeilko H., van den Berg, Leonard H., van Rheenen, Wouter, Veldink, Jan H., Harboe, Zitta B., Lundbo, Lene F., de Groot, Lisette C.P.G.M., van Schoor, Natasja M., van der Velde, Nathalie, Ängquist, Lars H., Sørensen, Thorkild I.A., Nohr, Ellen A., Mentzer, Alexander J., Mills, Tara C., Knight, Julian C., du Plessis, Mignon, Nzenze, Susan, Weiser, Jeffrey N., Parkhill, Julian, Madhi, Shabir, Benfield, Thomas, von Gottberg, Anne, van der Ende, Arie, Brouwer, Matthijs C., Barrett, Jeffrey C., Bentley, Stephen D., and van de Beek, Diederik

Published
2019

31. Contrasting approaches to genome-wide association studies impact the detection of resistance mechanisms in Staphylococcus aureus

Author

Wheeler, Nicole E., primary, Reuter, Sandra, additional, Chewapreecha, Claire, additional, Lees, John A., additional, Blane, Beth, additional, Horner, Carolyne, additional, Enoch, David, additional, Brown, Nicholas M., additional, Estée Török, M., additional, Aanensen, David M., additional, Parkhill, Julian, additional, and Peacock, Sharon J., additional

Published
2019
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34. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Author

Lees, John A., primary, Ferwerda, Bart, additional, Kremer, Philip H. C., additional, Wheeler, Nicole E., additional, Valls Serón, Mercedes, additional, Croucher, Nicholas J., additional, Gladstone, Rebecca A., additional, Bootsma, Hester J., additional, Rots, Nynke, additional, Wijmega-Monsuur, Alienke J., additional, Sanders, Elisabeth A. M., additional, Trzciński, Krzysztof, additional, Wyllie, Anne L., additional, Zwinderman, Aeilko H., additional, den Berg, Leonard H. van, additional, Rheenen, Wouter van, additional, H. Veldink, Jan, additional, Harboe, Zitta B., additional, Lundbo, Lene F., additional, Groot, Lisette C. P. G. M. de, additional, Schoor, Natasja M. van, additional, Velde, Nathalie van der, additional, Ängquist, Lars H., additional, Sørensen, Thorkild I.A., additional, Nohr, Ellen A., additional, Mentzer, Alexander J., additional, C. Mills, Tara, additional, Knight, Julian C., additional, du Plessis, Mignon, additional, Nzenze, Susan, additional, N. Weiser, Jeffrey, additional, Parkhill, Julian, additional, Madhi, Shabir, additional, Benfield, Thomas, additional, von Gottberg, Anne, additional, Ende, Arie van der, additional, Brouwer, Matthijs C., additional, Barrett, Jeffrey C., additional, Bentley, Stephen D., additional, and de Beek, Diederik van, additional

Published
2018
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38. Joint Sequencing of Human and Pathogen Genomes Reveals the Genetics of Pneumococcal Meningitis

Author

Lees, John, primary, Ferwerda, Bart, additional, Kremer, Philip H. C., additional, Wheeler, Nicole E., additional, Serón, Mercedes Valls, additional, Croucher, Nicholas J., additional, Gladstone, Rebecca A., additional, Bootsma, Hester J., additional, Rots, Nynke, additional, Wijmega-Monsuur, Alienke J., additional, Sanders, Elisabeth A. M., additional, Trzciński, Krzysztof, additional, Wyllie, Anne L., additional, Zwinderman, Aeilko H., additional, van den Berg, Leonard H., additional, Rheenen, Wouter van, additional, Veldink, Jan H., additional, Harboe, Zitta B., additional, Lundbo, Lene F., additional, de Groot, Lisette C. P. G. M., additional, van Schoor, Natasja M., additional, van der Velde, Nathalie, additional, Ängquist, Lars H., additional, Sørensen, Thorkild I. A., additional, Nohr, Ellen A., additional, Mentzer, Alexander J., additional, Mills, Tara C., additional, Knight, Julian C., additional, Plessis, Mignon du, additional, Nzenze, Susan, additional, Weiser, Jeffrey N., additional, Parkhill, Julian, additional, Madhi, Shabir, additional, Benfield, Thomas, additional, von Gottberg, Anne, additional, van der Ende, Arie, additional, Brouwer, Matthijs C., additional, Barrett, Jeffrey C., additional, Bentley, Stephen D., additional, and van de Beek, Diederik, additional

Published
2018
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45. Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling

Author

Lindgreen, Stinus, Umu, Sinan Ugur, Lai, Alicia Sook-Wei, Eldai, Hisham, Liu, Wenting, McGimpsey, Stephanie, Wheeler, Nicole E., Biggs, Patrick J., Thomson, Nick R., Barquist, Lars, Poole, Anthony M., Gardner, Paul P., Lindgreen, Stinus, Umu, Sinan Ugur, Lai, Alicia Sook-Wei, Eldai, Hisham, Liu, Wenting, McGimpsey, Stephanie, Wheeler, Nicole E., Biggs, Patrick J., Thomson, Nick R., Barquist, Lars, Poole, Anthony M., and Gardner, Paul P.

Published
2014

47. Robust Identification of Noncoding RNA from Transcriptomes Requires Phylogenetically-Informed Sampling

Author

Lindgreen, Stinus, primary, Umu, Sinan Uğur, additional, Lai, Alicia Sook-Wei, additional, Eldai, Hisham, additional, Liu, Wenting, additional, McGimpsey, Stephanie, additional, Wheeler, Nicole E., additional, Biggs, Patrick J., additional, Thomson, Nick R., additional, Barquist, Lars, additional, Poole, Anthony M., additional, and Gardner, Paul P., additional

Published
2014
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48. An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation

Author

Van Puyvelde, Sandra, Pickard, Derek, Vandelannoote, Koen, Heinz, Eva, Barbé, Barbara, De Block, Tessa, Clare, Simon, Coomber, Eve L., Harcourt, Katherine, Sridhar, Sushmita, Lees, Emily A., Wheeler, Nicole E., Klemm, Elizabeth J., Kuijpers, Laura, Mbuyi Kalonji, Lisette, Phoba, Marie-France, Falay, Dadi, Ngbonda, Dauly, Lunguya, Octavie, Jacobs, Jan, Dougan, Gordon, and Deborggraeve, Stijn

Subjects
631/114/739, 141, 45, 631/326/325/2482, article, 13/106, 45/23, 706/134, 38/70, 3. Good health, 692/699/255/1318, 631/326/22/1434, 64/60, 129
Abstract

Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.

49. An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation

Author

Van Puyvelde, Sandra, Pickard, Derek, Vandelannoote, Koen, Heinz, Eva, Barbé, Barbara, De Block, Tessa, Clare, Simon, Coomber, Eve L, Harcourt, Katherine, Sridhar, Sushmita, Lees, Emily A, Wheeler, Nicole E, Klemm, Elizabeth J, Kuijpers, Laura, Mbuyi Kalonji, Lisette, Phoba, Marie-France, Falay, Dadi, Ngbonda, Dauly, Lunguya, Octavie, Jacobs, Jan, Dougan, Gordon, and Deborggraeve, Stijn

Subjects
Salmonella typhimurium, Whole Genome Sequencing, THP-1 Cells, Microbial Sensitivity Tests, Azithromycin, Adaptation, Physiological, 3. Good health, Anti-Bacterial Agents, Cell Line, Mice, Inbred C57BL, Mice, Ciprofloxacin, Biofilms, Drug Resistance, Multiple, Bacterial, Democratic Republic of the Congo, Animals, Humans, Plasmids
Abstract

Bloodstream infections by Salmonella enterica serovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.

50. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Author

Lees, John A, Ferwerda, Bart, Kremer, Philip HC, Wheeler, Nicole E, Serón, Mercedes Valls, Croucher, Nicholas J, Gladstone, Rebecca A, Bootsma, Hester J, Rots, Nynke Y, Wijmega-Monsuur, Alienke J, Sanders, Elisabeth AM, Trzciński, Krzysztof, Wyllie, Anne L, Zwinderman, Aeilko H, Van Den Berg, Leonard H, Van Rheenen, Wouter, Veldink, Jan H, Harboe, Zitta B, Lundbo, Lene F, De Groot, Lisette CPGM, Van Schoor, Natasja M, Van Der Velde, Nathalie, Ängquist, Lars H, Sørensen, Thorkild IA, Nohr, Ellen A, Mentzer, Alexander J, Mills, Tara C, Knight, Julian C, Du Plessis, Mignon, Nzenze, Susan, Weiser, Jeffrey N, Parkhill, Julian, Madhi, Shabir, Benfield, Thomas, Von Gottberg, Anne, Van Der Ende, Arie, Brouwer, Matthijs C, Barrett, Jeffrey C, Bentley, Stephen D, and Van De Beek, Diederik

Subjects
Adult, Male, Genome, Human, Meningitis, Pneumococcal, Genetic Variation, Proteins, Middle Aged, 3. Good health, Streptococcus pneumoniae, Bacterial Proteins, Host-Pathogen Interactions, Humans, Female, Genetic Predisposition to Disease, Prospective Studies, Genome, Bacterial, Aged, Genome-Wide Association Study
Abstract

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.

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