Imperial College London

DrNicholasCroucher

Faculty of MedicineSchool of Public Health

Senior Lecturer in Bacterial Genomics
 
 
 
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Contact

 

+44 (0)20 7594 3820n.croucher

 
 
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Location

 

UG5Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

59 results found

Apagyi KJ, Fraser C, Croucher NJ, 2018, Transformation Asymmetry and the Evolution of the Bacterial Accessory Genome, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 35, Pages: 575-581, ISSN: 0737-4038

JOURNAL ARTICLE

Cremers AJH, Mobegi FM, van der Gaast-de Jongh C, van Weert M, van Opzeeland FJ, Vehkala M, Knol MJ, Bootsma HJ, Välimäki N, Croucher NJ, Meis JF, Bentley S, van Hijum SAFT, Corander J, Zomer AL, Ferwerda G, de Jonge MIet al., 2018, The Contribution of Genetic Variation of Streptococcus Pneumoniae to the Clinical Manifestation of Invasive Pneumococcal Disease., Clin Infect Dis

Background: Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype. Methods: The index cohort consisted of 349 patients admitted to two Dutch hospitals between 2000-2011 with pneumococcal bacteraemia. We performed genome-wide association studies to identify pneumococcal lineages, genes and allelic variants associated with 23 clinical IPD phenotypes. The identified associations were validated in a nationwide (n=482) and a post-pneumococcal vaccination cohort (n=121). The contribution of confirmed pneumococcal genotypes to the clinical IPD phenotype, relative to known clinical predictors, was tested by regression analysis. Results: Among IPD patients, the presence of pneumococcal gene slaA was a nationwide confirmed independent predictor of meningitis (OR=10.5, p=0.001, 5% presence), as was sequence cluster 9 (predominant serotype 7F, OR=3.68, p=0.057, 11% presence). A set of 4 pneumococcal genes co-located on a prophage was a confirmed independent predictor of 30-day mortality (OR=3.4, p=0.003, 48% presence). We could detect the pneumococcal variants of concern in these patients' blood samples. Conclusions: In this study, knowledge of pneumococcal genotypic variants improved the clinical risk assessment for detrimental manifestations of IPD. This provides us with novel opportunities to target, anticipate or avert the pathogenic effects related to particular pneumococcal variants, and indicates that information on pneumococcal genotype is important for the diagnostic and treatment strategy in IPD. Ongoing surveillance is warranted to monitor the clinical value of information on pneumococcal variants in dynamic microbial and susceptible host populations.

JOURNAL ARTICLE

Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM, Harris SRet al., 2018, Phandango: an interactive viewer for bacterial population genomics, BIOINFORMATICS, Vol: 34, Pages: 292-293, ISSN: 1367-4803

JOURNAL ARTICLE

Campo JJ, Croucher NJ, Turner P, Tate A, Le T, Pablo J, Hung C, Teng A, Hanage WP, Lipsitch M, Goldblatt D, Alderson M, Liang Xet al., 2017, UNDERSTANDING THE IMMUNE RESPONSE TO STREPTOCOCCUS PNEUMONIAE FROM VACCINATION AND CARRIAGE ON A PROTEOME SCALE, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 367-367, ISSN: 0002-9637

CONFERENCE PAPER

Corander J, Fraser C, Gutmann MU, Arnold B, Hanage WP, Bentley SD, Lipsitch M, Croucher NJet al., 2017, Frequency-dependent selection in vaccine-associated pneumococcal population dynamics, NATURE ECOLOGY & EVOLUTION, Vol: 1, Pages: 1950-1960, ISSN: 2397-334X

JOURNAL ARTICLE

Croucher NJ, Campo JJ, Le TQ, Liang X, Bentley SD, Hanage WP, Lipsitch Met al., 2017, Diverse evolutionary patterns of pneumococcal antigens identified by pangenome-wide immunological screening, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 114, Pages: E357-E366, ISSN: 0027-8424

JOURNAL ARTICLE

De Ste Croix M, Vacca I, Kwun MJ, Ralph JD, Bentley SD, Haigh R, Croucher NJ, Oggioni MRet al., 2017, Phase-variable methylation and epigenetic regulation by type I restriction-modification systems, FEMS MICROBIOLOGY REVIEWS, Vol: 41, Pages: S3-S15, ISSN: 0168-6445

JOURNAL ARTICLE

Lees JA, Croucher NJ, Goldblatt D, Nosten F, Parkhill J, Turner C, Turner P, Bentley SDet al., 2017, Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration, ELIFE, Vol: 6, ISSN: 2050-084X

JOURNAL ARTICLE

Lees JA, Kremer PHC, Manso AS, Croucher NJ, Ferwerda B, Seron MV, Oggioni MR, Parkhill J, Brouwer MC, van der Ende A, van de Beek D, Bentley SDet al., 2017, Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis, MICROBIAL GENOMICS, Vol: 3, ISSN: 2057-5858

JOURNAL ARTICLE

Lehtinen S, Blanquart F, Croucher NJ, Turner P, Lipsitch M, Fraser Cet al., 2017, Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 114, Pages: 1075-1080, ISSN: 0027-8424

JOURNAL ARTICLE

Mostowy R, Croucher NJ, Andam CP, Corander J, Hanage WP, Marttinen Pet al., 2017, Efficient Inference of Recent and Ancestral Recombination within Bacterial Populations, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 34, Pages: 1167-1182, ISSN: 0737-4038

JOURNAL ARTICLE

Mostowy RJ, Croucher NJ, De Maio N, Chewapreecha C, Salter SJ, Turner P, Aanensen DM, Bentley SD, Didelot X, Fraser Cet al., 2017, Pneumococcal Capsule Synthesis Locus cps as Evolutionary Hotspot with Potential to Generate Novel Serotypes by Recombination, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 34, Pages: 2537-2554, ISSN: 0737-4038

JOURNAL ARTICLE

Skwark MJ, Croucher NJ, Puranen S, Chewapreecha C, Pesonen M, Xu YY, Turner P, Harris SR, Beres SB, Musser JM, Parkhill J, Bentley SD, Aurell E, Corander Jet al., 2017, Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis, PLOS GENETICS, Vol: 13, ISSN: 1553-7404

JOURNAL ARTICLE

Croucher NJ, Mostowy R, Wymant C, Turner P, Bentley SD, Fraser Cet al., 2016, Horizontal DNA Transfer Mechanisms of Bacteria as Weapons of Intragenomic Conflict, PLOS BIOLOGY, Vol: 14, ISSN: 1545-7885

JOURNAL ARTICLE

Lees JA, Vehkala M, Valimaki N, Harris SR, Chewapreecha C, Croucher NJ, Marttinen P, Davies MR, Steer AC, Tong SYC, Honkela A, Parkhill J, Bentley SD, Corander Jet al., 2016, Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723

JOURNAL ARTICLE

Chang Q, Stevenson AE, Croucher NJ, Lee GM, Pelton SI, Lipsitch M, Finkelstein JA, Hanage WPet al., 2015, Stability of the pneumococcal population structure in Massachusetts as PCV13 was introduced, BMC INFECTIOUS DISEASES, Vol: 15, ISSN: 1471-2334

JOURNAL ARTICLE

Croucher NJ, Didelot X, 2015, The application of genomics to tracing bacterial pathogen transmission, CURRENT OPINION IN MICROBIOLOGY, Vol: 23, Pages: 62-67, ISSN: 1369-5274

JOURNAL ARTICLE

Croucher NJ, Finkelstein JA, Pelton SI, Parkhill J, Bentley SD, Lipsitch M, Hanage WPet al., 2015, Population genomic datasets describing the post-vaccine evolutionary epidemiology of Streptococcus pneumoniae, SCIENTIFIC DATA, Vol: 2, ISSN: 2052-4463

JOURNAL ARTICLE

Croucher NJ, Kagedan L, Thompson CM, Parkhill J, Bentley SD, Finkelstein JA, Lipsitch M, Hanage WPet al., 2015, Selective and Genetic Constraints on Pneumococcal Serotype Switching, PLOS GENETICS, Vol: 11, ISSN: 1553-7404

JOURNAL ARTICLE

Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA, Bentley SD, Parkhill J, Harris SRet al., 2015, Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins, NUCLEIC ACIDS RESEARCH, Vol: 43, ISSN: 0305-1048

JOURNAL ARTICLE

Li Y, Croucher NJ, Thompson CM, Trzcinski K, Hanage WP, Lipsitch Met al., 2015, Identification of pneumococcal colonization determinants in the stringent response pathway facilitated by genomic diversity, BMC GENOMICS, Vol: 16, ISSN: 1471-2164

JOURNAL ARTICLE

Marttinen P, Croucher NJ, Gutmann MU, Corander J, Hanage WPet al., 2015, Recombination produces coherent bacterial species clusters in both core and accessory genomes, MICROBIAL GENOMICS, Vol: 1, ISSN: 2057-5858

JOURNAL ARTICLE

Chewapreecha C, Harris SR, Croucher NJ, Turner C, Marttinen P, Cheng L, Pessia A, Aanensen DM, Mather AE, Page AJ, Salter SJ, Harris D, Nosten F, Goldblatt D, Corander J, Parkhill J, Turner P, Bentley SDet al., 2014, Dense genomic sampling identifies highways of pneumococcal recombination, NATURE GENETICS, Vol: 46, Pages: 305-+, ISSN: 1061-4036

JOURNAL ARTICLE

Chewapreecha C, Marttinen P, Croucher NJ, Salter SJ, Harris SR, Mather AE, Hanage WP, Goldblatt D, Nosten FH, Turner C, Turner P, Bentley SD, Parkhill Jet al., 2014, Comprehensive Identification of Single Nucleotide Polymorphisms Associated with Beta-lactam Resistance within Pneumococcal Mosaic Genes, PLOS GENETICS, Vol: 10, ISSN: 1553-7404

JOURNAL ARTICLE

Croucher NJ, Chewapreecha C, Hanage WP, Harris SR, McGee L, van der Linden M, Song J-H, Ko KS, de Lencastre H, Turner C, Yang F, Sa-Leao R, Beall B, Klugman KP, Parkhill J, Turner P, Bentley SDet al., 2014, Evidence for Soft Selective Sweeps in the Evolution of Pneumococcal Multidrug Resistance and Vaccine Escape, GENOME BIOLOGY AND EVOLUTION, Vol: 6, Pages: 1589-1602, ISSN: 1759-6653

JOURNAL ARTICLE

Croucher NJ, Coupland PG, Stevenson AE, Callendrello A, Bentley SD, Hanage WPet al., 2014, Diversification of bacterial genome content through distinct mechanisms over different timescales, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723

JOURNAL ARTICLE

Croucher NJ, Hanage WP, Harris SR, McGee L, van der Linden M, de Lencastre H, Sa-Leao R, Song J-H, Ko KS, Beall B, Klugman KP, Parkhill J, Tomasz A, Kristinsson KG, Bentley SDet al., 2014, Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone, BMC BIOLOGY, Vol: 12, ISSN: 1741-7007

JOURNAL ARTICLE

Croucher NJ, Klugman KP, 2014, The Emergence of Bacterial "Hopeful Monsters", MBIO, Vol: 5, ISSN: 2150-7511

JOURNAL ARTICLE

Lee GM, Kleinman K, Pelton SI, Hanage W, Huang SS, Lakoma M, Dutta-Linn M, Croucher NJ, Stevenson A, Finkelstein JAet al., 2014, Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts., J Pediatric Infect Dis Soc, Vol: 3, Pages: 23-32

BACKGROUND: In April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade. METHODS: Nasopharyngeal swabs were obtained from children 0 to <7 years of age and seen by primary care providers for well child or acute illness visits in 2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes. Changes in colonization and impact of PCV13 were assessed using generalized linear mixed models, adjusting for known risk factors and accounting for clustering by community. RESULTS: Introduction of PCV13 did not affect the rate of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13 serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained the second most common serotype in 2011, although a decline from 2009 was observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin (10%) nonsusceptibility were commonly identified, concentrated among a small number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children 6-23 months old, colonization with PCV13 serotypes was lower among recipients of PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not observed in 6- to 23-month-old children with a concomitant respiratory tract infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old (adjusted OR, 1.17; 95% CI, 0.58, 2.34). CONCLUSIONS: 13-Valent pneumococcal conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes among children 6-23 months old, b

JOURNAL ARTICLE

Mostowy R, Croucher NJ, Hanage WP, Harris SR, Bentley S, Fraser Cet al., 2014, Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution, PLOS GENETICS, Vol: 10, ISSN: 1553-7390

JOURNAL ARTICLE

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