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.
Corander J, Fraser C, Gutmann MU, et 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.
Croucher NJ, Campo JJ, Le TQ, et 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
De Ste Croix M, Vacca I, Kwun MJ, et 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
Lees JA, Croucher NJ, Goldblatt D, et al., 2017, Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration, ELIFE, Vol: 6, ISSN: 2050-084X
Lees JA, Kremer PHC, Manso AS, et 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.
Lehtinen S, Blanquart F, Croucher NJ, et 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
Mostowy R, Croucher NJ, Andam CP, et al., 2017, Efficient Inference of Recent and Ancestral Recombination within Bacterial Populations, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 34, Pages: 1167-1182, ISSN: 0737-4038
Mostowy RJ, Croucher NJ, De Maio N, et 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
Skwark MJ, Croucher NJ, Puranen S, et al., 2017, Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis, PLOS GENETICS, Vol: 13, ISSN: 1553-7404
Croucher NJ, Mostowy R, Wymant C, et al., 2016, Horizontal DNA Transfer Mechanisms of Bacteria as Weapons of Intragenomic Conflict, PLOS BIOLOGY, Vol: 14, ISSN: 1545-7885
Lees JA, Vehkala M, Valimaki N, et al., 2016, Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723
Chang Q, Stevenson AE, Croucher NJ, et al., 2015, Stability of the pneumococcal population structure in Massachusetts as PCV13 was introduced, BMC INFECTIOUS DISEASES, Vol: 15, ISSN: 1471-2334
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
Croucher NJ, Finkelstein JA, Pelton SI, et al., 2015, Population genomic datasets describing the post-vaccine evolutionary epidemiology of Streptococcus pneumoniae, SCIENTIFIC DATA, Vol: 2, ISSN: 2052-4463
Croucher NJ, Kagedan L, Thompson CM, et al., 2015, Selective and Genetic Constraints on Pneumococcal Serotype Switching, PLOS GENETICS, Vol: 11, ISSN: 1553-7404
Croucher NJ, Page AJ, Connor TR, et al., 2015, Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins, NUCLEIC ACIDS RESEARCH, Vol: 43, ISSN: 0305-1048
Li Y, Croucher NJ, Thompson CM, et al., 2015, Identification of pneumococcal colonization determinants in the stringent response pathway facilitated by genomic diversity, BMC GENOMICS, Vol: 16, ISSN: 1471-2164
Marttinen P, Croucher NJ, Gutmann MU, et 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.
Chewapreecha C, Harris SR, Croucher NJ, et al., 2014, Dense genomic sampling identifies highways of pneumococcal recombination, NATURE GENETICS, Vol: 46, Pages: 305-+, ISSN: 1061-4036
Chewapreecha C, Marttinen P, Croucher NJ, et al., 2014, Comprehensive Identification of Single Nucleotide Polymorphisms Associated with Beta-lactam Resistance within Pneumococcal Mosaic Genes, PLOS GENETICS, Vol: 10, ISSN: 1553-7404
Croucher NJ, Chewapreecha C, Hanage WP, et 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
Croucher NJ, Coupland PG, Stevenson AE, et al., 2014, Diversification of bacterial genome content through distinct mechanisms over different timescales, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
Croucher NJ, Hanage WP, Harris SR, et al., 2014, Variable recombination dynamics during the emergence, transmission and 'disarming' of a multidrug-resistant pneumococcal clone, BMC BIOLOGY, Vol: 12, ISSN: 1741-7007
Croucher NJ, Klugman KP, 2014, The Emergence of Bacterial "Hopeful Monsters", MBIO, Vol: 5, ISSN: 2150-7511
Lee GM, Kleinman K, Pelton SI, et 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
Mostowy R, Croucher NJ, Hanage WP, et al., 2014, Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution, PLOS GENETICS, Vol: 10, ISSN: 1553-7390
Tasoulis S, Cheng L, Valimaki N, et al., 2014, Random Projection Based Clustering for Population Genomics, IEEE International Conference on Big Data, Publisher: IEEE, Pages: 675-682
Croucher NJ, Finkelstein JA, Pelton SI, et al., 2013, Population genomics of post-vaccine changes in pneumococcal epidemiology, NATURE GENETICS, Vol: 45, Pages: 656-+, ISSN: 1061-4036
Croucher NJ, Harris SR, Grad YH, et al., 2013, Bacterial genomes in epidemiology-present and future, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.