Predicting evolution using frequency-dependent selection in bacterial populations

Azarian, Taj; Martinez, Pamela P.; Arnold, Brian J.; Grant, Lindsay R.; Corander, Jukka; Fraser, Christophe; Croucher, Nicholas J.; Hammitt, Laura L.; Reid, Raymond; Santosham, Mathuram; Weatherholtz, Robert; Bentley, Stephen D.; O’Brien, Katherine L.; Lipsitch, Marc; Hanage, William P.

doi:10.1101/420315

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…Preservation of gene frequencies in the population through negative frequency-dependent selection has been shown to exist in pneumococci, and can be used to predict serotype replacement in carriage [16,36]. This suggests that the gene content of a GPSCs influences whether it will undergo replacement or expansion after vaccine perturbation.…”

Section: Discussionmentioning

confidence: 99%

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

et al. 2019

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Background Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background. Methods Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage. Findings The combined collections ( n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction. Penicillin and multidrug resistance were higher ( p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R 2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor ( p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13). We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed. Interpretation We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.

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Section: Discussionmentioning

confidence: 99%

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

et al. 2019

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“…Recent work has shown that models that incorporate genomics or clonal groups can forecast which serotypes will be successful after vaccination [19, 20, 31]. Future work could combine the results of this study with new genomics studies, directly incorporating information on the fitness of a serotype (e.g., as calculated by Azarian) in these models, or this type of model structure could be used to benchmark alternative modeling approaches.…”

Section: Discussionmentioning

confidence: 99%

“…However, when the goal is to examine emerging serotypes, it is important to consider individual serotypes. Recent work has used genomic data with models of negative frequency-dependent selection to quantify post-vaccine expansion patterns [19, 20]. However, whole genome sequence data are not always widely available, and their interpretation is complex.…”

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confidence: 99%

Evaluating post-vaccine expansion patterns of pneumococcal serotypes

Phillips¹,

Warren²,

Givon-Lavi

et al. 2020

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Streptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.

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“…We then consider the response of repertoire structure as a manifestation of whether the influence of NFDS recovers quickly after the intervention. We end by drawing plausible analogies and implications for other ecological systems (Forrister et al, 2019a;Azarian et al, 2019), in particular for communities of species under stabilizing competition, Janzen-Connell mechanisms of coexistence and other forms of balancing selection.…”

Section: Introductionmentioning

confidence: 99%

Frequency-dependent competition between strains imparts resilience to perturbations in a model ofPlasmodium falciparummalaria transmission

Pilosof

Tiedje

et al. 2020

Preprint

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In high-transmission endemic regions, local populations of Plasmodium falciparum exhibit vast diversity of the var genes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires (strains), in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the resilience of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more resilient under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the resulting resilience to perturbations, intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence.

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Predicting evolution using frequency-dependent selection in bacterial populations

Cited by 10 publications

References 54 publications

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

Evaluating post-vaccine expansion patterns of pneumococcal serotypes

Frequency-dependent competition between strains imparts resilience to perturbations in a model ofPlasmodium falciparummalaria transmission

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