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

56 results found

Apagyi KJ, Fraser C, Croucher NJ, 2017, Transformation asymmetry and the evolution of the bacterial accessory genome., Mol Biol Evol

Bacterial transformation can insert or delete genomic islands (GIs), depending on the donor and recipient genotypes, if an homologous recombination spans the GI's integration site and includes sufficiently long flanking homologous arms. Combining mathematical models of recombination with experiments using pneumococci found GI insertion rates declined geometrically with the GI's size. The decrease in acquisition frequency with length (1.08x10-3 bp-1) was higher than a previous estimate of the analogous rate at which core genome recombinations terminated. Although most efficient for shorter GIs, transformation-mediated deletion frequencies did not vary consistently with GI length, with removal of 10 kb GIs approximately 50% as efficient as acquisition of base substitutions. Fragments of two kilobases, typical of transformation event sizes, could drive all these deletions independent of island length. The strong asymmetry of transformation, and its capacity to efficiently remove GIs, suggests non-mobile accessory loci will decline in frequency without preservation by selection.

JOURNAL ARTICLE

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., Nat Ecol Evol, Vol: 1, Pages: 1950-1960

Many bacterial species are composed of multiple lineages distinguished by extensive variation in gene content. These often cocirculate in the same habitat, but the evolutionary and ecological processes that shape these complex populations are poorly understood. Addressing these questions is particularly important for Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen, because the changes in population structure associated with the recent introduction of partial-coverage vaccines have substantially reduced pneumococcal disease. Here we show that pneumococcal lineages from multiple populations each have a distinct combination of intermediate-frequency genes. Functional analysis suggested that these loci may be subject to negative frequency-dependent selection (NFDS) through interactions with other bacteria, hosts or mobile elements. Correspondingly, these genes had similar frequencies in four populations with dissimilar lineage compositions. These frequencies were maintained following substantial alterations in lineage prevalences once vaccination programmes began. Fitting a multilocus NFDS model of post-vaccine population dynamics to three genomic datasets using Approximate Bayesian Computation generated reproducible estimates of the influence of NFDS on pneumococcal evolution, the strength of which varied between loci. Simulations replicated the stable frequency of lineages unperturbed by vaccination, patterns of serotype switching and clonal replacement. This framework highlights how bacterial ecology affects the impact of clinical interventions.

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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

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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

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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

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Lees JA, Kremer PHC, Manso AS, Croucher NJ, Ferwerda B, SerĂ³n 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., Microb Genom, Vol: 3, ISSN: 2057-5858

Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood-brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness.

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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

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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

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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

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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

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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

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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

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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

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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., Microb Genom, Vol: 1, ISSN: 2057-5858

BACKGROUND: Population samples show bacterial genomes can be divided into a core of ubiquitous genes and accessory genes that are present in a fraction of isolates. The ecological significance of this variation in gene content remains unclear. However, microbiologists agree that a bacterial species should be 'genomically coherent', even though there is no consensus on how this should be determined. RESULTS: We use a parsimonious model combining diversification in both the core and accessory genome, including mutation, homologous recombination (HR) and horizontal gene transfer (HGT) introducing new loci, to produce a population of interacting clusters of strains with varying genome content. New loci introduced by HGT may then be transferred on by HR. The model fits well to a systematic population sample of 616 pneumococcal genomes, capturing the major features of the population structure with parameter values that agree well with empirical estimates. CONCLUSIONS: The model does not include explicit selection on individual genes, suggesting that crude comparisons of gene content may be a poor predictor of ecological function. We identify a clearly divergent subpopulation of pneumococci that are inconsistent with the model and may be considered genomically incoherent with the rest of the population. These strains have a distinct disease tropism and may be rationally defined as a separate species. We also find deviations from the model that may be explained by recent population bottlenecks or spatial structure.

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

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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

Tasoulis S, Cheng L, Valimaki N, Croucher NJ, Harris SR, Hanage WP, Roos T, Corander Jet al., 2014, Random Projection Based Clustering for Population Genomics, IEEE International Conference on Big Data, Publisher: IEEE, Pages: 675-682

CONFERENCE PAPER

Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM, Parkhill J, Bentley SD, Hanage WP, Lipsitch Met al., 2013, Population genomics of post-vaccine changes in pneumococcal epidemiology, NATURE GENETICS, Vol: 45, Pages: 656-+, ISSN: 1061-4036

JOURNAL ARTICLE

Croucher NJ, Harris SR, Grad YH, Hanage WPet al., 2013, Bacterial genomes in epidemiology-present and future, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436

JOURNAL ARTICLE

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