Rapid Pneumococcal Evolution in Response to Clinical Interventions

Croucher, Nicholas J.; Harris, Simon R.; Fraser, Christophe; Quail, Michael A.; Burton, John H.; Linden, Mark van der; McGee, Lesley; Gottberg, Anne von; Song, Jae Hoon; Ko, Kwan Soo; Pichon, Bruno; Baker, Stephen; Parry, Christopher M.; Lambertsen, Lotte; Shahinas, Dea; Pillai, Dylan R.; Mitchell, Tim; Dougan, Gordon; Tomasz, Alexander; Klugman, Keith P.; Parkhill, Julian; Hanage, William P.; Bentley, Stephen D.

doi:10.1126/science.1198545

Cited by 820 publications

(1,030 citation statements)

References 31 publications

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“…When we included branch lengths in the distance measure ( λ = 1 in the KC metric), very short branch lengths contribute far less to the tree distance than longer lengths, and the ribosomal genes are no longer outliers. Many of the furthest gene trees from the core genome tree are from genes known to be involved in recombination events 46 , as shown in Supplementary Table 1 ( Supplementary File 1). Recombinations result in a large number of SNPs against a reference; because phylogenetic methods assume vertical evolution, recombination tends to inflate estimated branch lengths.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Lees¹,

Kendall²,

Parkhill³

et al. 2018

Wellcome Open Res

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Background: Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods: We simulated data from a defined “true tree” using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions. We also used real data from Streptococcus pneumoniae alignments to compare individual core gene trees to a core genome tree. Results: We found that, as expected, maximum likelihood trees from good quality alignments were the most accurate, but also the most computationally intensive. Using less accurate phylogenetic reconstruction methods, we were able to obtain results of comparable accuracy; we found that approximate results can rapidly be obtained using genetic distance based methods. In real data we found that highly conserved core genes, such as those involved in translation, gave an inaccurate tree topology, whereas genes involved in recombination events gave inaccurate branch lengths. We also show a tree-of-trees, relating the results of different phylogenetic reconstructions to each other. Conclusions: We recommend three approaches, depending on requirements for accuracy and computational time. Quicker approaches that do not perform full maximum likelihood optimisation may be useful for many analyses requiring a phylogeny, as generating a high quality input alignment is likely to be the major limiting factor of accurate tree topology. We have publicly released our simulated data and code to enable further comparisons.

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Section: Resultsmentioning

confidence: 99%

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Lees¹,

Kendall²,

Parkhill³

et al. 2018

Wellcome Open Res

Self Cite

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“…After the introduction of the PCV7 vaccine there was a significant increase in strain 19A, a non-vaccine type strain. 29 Importantly, the amount of antibiotic-resistance in this serotype also increased. 30 Serotypes 6A, 6B, 9V, 14, 15A, 19F, and 23F have also shown the most antibiotic-resistance to penicillin and erythromycin, with many of these serotypes being included in the vaccines.…”

Section: Characteristics Of the Bacteriummentioning

confidence: 96%

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Wantuch

Avci

2018

Human Vaccines & Immunotherapeutics

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Streptococcus pneumoniae is a major human bacterial pathogen responsible for millions of deaths each year and significantly more illnesses worldwide. With over 90 different serotypes, providing effective vaccine programs has been a continuing challenge. Since 1983, the world has been introduced to four different pneumococcal vaccines (PPSV23, PCV7, PCV10, and PCV13) each with their own complications and successes. Since vaccination programs began, a decrease in the overall rate of pneumococcal pneumonia and associated diseases has been observed, notably in higher risk populations. However, with a decrease in incidence of vaccine type pneumococcal serotypes, increases in non-vaccine serotypes of the bacteria have been observed along with serotype switching. Additionally, a rise in antibiotic resistant strains of S. pneumoniae is noted. Here we discuss both the positive and negative clinical manifestations of pneumonia vaccine programs and discuss the challenges in pneumococcal vaccine design.

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“…However, the reliability of this index is questionable, because it may vary greatly among studies (35). For example, in Streptococcus pneumoniae the r/m has been estimated at 66 by MLST (38) but at 7.2 by WGS (39).…”

Section: Some Problems With the Semiclonal/epidemic Clonality Modelmentioning

confidence: 99%

How clonal are Neisseria species? The epidemic clonality model revisited

Tibayrenc

Ayala

2015

Proc. Natl. Acad. Sci. U.S.A.

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The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria lactamica are often regarded as highly recombining bacteria. N. meningitidis has been considered a paradigmatic case of the "semiclonal model" or of "epidemic clonality," demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that N. meningitidis fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (i) the proposed way to distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of N. meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model.T he clonality/sexuality controversy in microbiology has gone on for more than 35 y in bacteria (1, 2) as well as in parasitic protozoa (3-6). Early on, several instances of bacterial and parasitic species were removed from the clonal paradigm and instead were considered as "highly recombining" (5). The controversy now can be reconsidered in the light of major results obtained with modern technologies, such as whole-genome sequencing (WGS), single nucleotide polymorphism analysis (SNP), microarrays, and megacomputing, which have made possible considerable advances in evolutionary biology, population genetics, and molecular epidemiology. We reconsider the issue of the population structure of Neisseria meningitidis in the light of these advances.N. meningitidis and the "Epidemic Clonality" and "Semiclonal" Models The molecular epidemiology and population genetics of N. meningitidis, a major agent of meningitis, has received much attention. Thousands of strains have been characterized by various markers, including multilocus enzyme electrophoresis (MLEE), multilocus sequence analysis (MLST), random primed polymorphic DNA (RAPD), and WGS and SNP analysis (reviewed in ref. 7). Pioneering MLEE studies showed that, although this pathogen has a drastically restricted ecological niche, infecting only humans, it exhibits considerable genetic diversity, suggesting that N. meningitidis undergoes extensive genetic recombination. However, the natural populations of this species consistently exhibit a strong linkage disequilibrium (LD), i.e., nonrandom association between genotypes at different loci (8). To reconcile these two observations, which at first appear mutually inconsistent, Maynard Smith et al. (5) proposed the epidemic clonality model, which states that the species under study undergoes occasional bouts of clonal propagation in an otherwise recombining population structure. "Epidemic" clones, which are greatly favored by both positive and purging selection, are repeatedly represented in natural populations as ...

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Rapid Pneumococcal Evolution in Response to Clinical Interventions

Cited by 820 publications

References 31 publications

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

How clonal are Neisseria species? The epidemic clonality model revisited

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