Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

As infectious agents of bacteria and vehicles of horizontal gene transfer, plasmids play a key role in bacterial ecology and evolution. Plasmid dynamics are shaped not only by plasmid–host interactions but also by ecological interactions between plasmid variants. These interactions are complex: plasmids can co-infect the same cell and the consequences for the co-resident plasmid can be either beneficial or detrimental. Many of the biological processes that govern plasmid co-infection—from systems that exclude infection by other plasmids to interactions in the regulation of plasmid copy number—are well characterized at a mechanistic level. Modelling plays a central role in translating such mechanistic insights into predictions about plasmid dynamics and the impact of these dynamics on bacterial evolution. Theoretical work in evolutionary epidemiology has shown that formulating models of co-infection is not trivial, as some modelling choices can introduce unintended ecological assumptions. Here, we review how the biological processes that govern co-infection can be represented in a mathematical model, discuss potential modelling pitfalls, and analyse this model to provide general insights into how co-infection impacts ecological and evolutionary outcomes. In particular, we demonstrate how beneficial and detrimental effects of co-infection give rise to frequency-dependent selection on plasmid variants. This article is part of the theme issue ‘The secret lives of microbial mobile genetic elements’.

Evolutionary epidemiology of a zoonosis

Cryptosporidium parvum is a global zoonoses and a major cause of diarrhoea in humans and ruminants. The parasite's life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. Here, we compare 32 whole genome sequences from human- and ruminant-derived parasite isolates collected across Europe, Egypt and China. We identify three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. We show that: (1) recombination occurs between ruminant isolates into human isolates; (2) these recombinant regions can be passed on to other human subtypes through gene flow and population admixture; (3) there have been multiple genetic exchanges, and all are likely recent; (4) putative virulence genes are significantly enriched within these genetic exchanges, and (5) this results in an increase in their nucleotide diversity. We carefully dissect the phylogenetic sequence of two genetic exchanges, illustrating the long-term evolutionary consequences of these events. Our results suggest that increased globalisation and close human-animal contacts increase the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spillover and spillback events. We discuss how this can provide a novel substrate for natural selection at genes involved in host-parasite interactions, thereby potentially altering the dynamic coevolutionary equilibrium in the Red Queens arms race.

Regulated Emergence of the African swine fever virus: B646L (p72) Gene Based Bayesian Coalescent Analysis

African swine fever virus (ASFV) belongs to the genus of virus of the Asfaviridae family. ASFV infection causes hemorrhage and high death rate hence increased loss to the swine community. It is a complex infectious disease of swine, which constitutes devastating impacts on animal health and the economy of the pig farmers. It has been confirmed that virus infections has been spreading in swine population for many years. In this study, the evolutionary epidemiology analysis of ASF virus from the geographical regions Africa, Europe, and Asia, respectively were retrieved from GenBank for the analysis. The nucleotide gene sequences of the viral protein p72 encoded by B646L gene published during 1960-2020 was taken in to study. The Bayesian skyline model with uncorrelated randomized clock model was employed to reconstruct the evolutionary history of the virus, to identify virus population demographics. Results of the analysis suggested that ASFV exhibited a high evolutionary rate, as the divergence caused reduction in the population in the recent years. The B646L gene of ASFV had an evolutionary rate of 4.13 X 10-6 substitution/site/year and the tMRCA as 3.15 x 105 with 95 percent HPD range in years (2.4 x 104 to 1.23 x 106) was obtained. In conclusion, the evolutionary study of ASFV with p72 protein from the ASFV of the B646L genes indicated that they evolved at a faster rate and plays a major role in the evolutionary process. Further, this study may help in designing or developing vaccines to control the spread of the disease.

Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

As infectious agents of bacteria and vehicles of horizontal gene transfer, plasmids play a key role in bacterial ecology and evolution. Plasmid dynamics are shaped not only by plasmid-host interactions, but also by ecological interactions between plasmid variants. These interactions are complex: plasmids can co-infect the same host cell and the consequences for the co-resident plasmid can be either beneficial or detrimental. Many of the biological processes that govern plasmid co-infection--from systems to exclude infection by other plasmids to interactions in the regulation of plasmid copy number per cell--are well characterised at a mechanistic level. Modelling plays a central role in translating such mechanistic insights into predictions about plasmid dynamics, and in turn, the impact of these dynamics on bacterial evolution. Theoretical work in evolutionary epidemiology has shown that formulating models of co-infection is not trivial, as some modelling choices can introduce unintended ecological assumptions. Here, we review how the biological processes that govern co-infection can be represented in a mathematical model, discuss potential modelling pitfalls, and analyse this model to provide general insights into how co-infection impacts eco-evolutionary outcomes. In particular, we demonstrate how beneficial and detrimental effects of co-infection give rise to frequency-dependent selection.

Global emergence and evolutionary dynamics of bluetongue virus

Bluetongue virus (BTV) epidemics are responsible for worldwide economic losses of up to US$ 3 billion. Understanding the global evolutionary epidemiology of BTV is critical in designing intervention programs. Here we employed phylodynamic models to quantify the evolutionary characteristics, spatiotemporal origins, and multi-host transmission dynamics of BTV across the globe. We inferred that goats are the ancestral hosts for BTV but are less likely to be important for cross-species transmission, sheep and cattle continue to be important for the transmission and maintenance of infection between other species. Our models pointed to China and India, countries with the highest population of goats, as the likely ancestral country for BTV emergence and dispersal worldwide over 1000 years ago. However, the increased diversification and dispersal of BTV coincided with the initiation of transcontinental livestock trade after the 1850s. Our analysis uncovered important epidemiological aspects of BTV that may guide future molecular surveillance of BTV.

From Vaccine to Pathogen: Modeling Sabin 2 Vaccine Virus Reversion and Evolutionary Epidemiology

The oral poliovirus vaccines (OPV) are one of most effective disease eradication tools in public health. However, the Sabin 2 vaccine strain can revert attenuation and cause outbreaks of circulating, vaccine-derived poliovirus (cVDPV2) that are clinically indistinguishable from wild poliovirus (WPV). Accurately assessing cVDP2 risk requires disentangling the complex interaction between epidemiology and evolutionary biology. Here, we developed a Sabin 2 reversion model that simulates the reversion of Sabin 2 to WPV based on the clinical differences in shedding duration and infectiousness between individuals vaccinated with Sabin 2 and those infected with wild poliovirus. Genetic reversion is informed by a canonical reversion pathway defined by three gatekeeper mutations (A481G, U2909C, and U398C) and the accumulation of genetic load from deleterious nonsynonymous mutations. Our model captures essential aspects of both phenotypic and molecular evolution and simulates transmission using a multiscale transmission model that consolidates the relationships among immunity, susceptibility, and transmission risk. We show that despite the rapid reversion of Sabin 2, cVDPV2 outbreaks can be controlled by maintaining high levels of population-level immunity and sanitation. Supplementary immunization activities must maintain high vaccine coverage to prevent future cVDPV2 outbreaks in the targeted intervention zone, but declining global immunity against Sabin 2 makes them increasingly risky to implement in poor sanitation regions regardless of historical immunization activity. A combined strategy of assessing and improving sanitation levels in conjunction with high coverage vaccination campaigns will limit future cVDPV2 emergence and spread.Significance StatementSince the withdrawal of the Sabin 2 oral poliovirus vaccine (OPV2), circulating vaccine-derived poliovirus outbreaks caused by the genetic reversion of Sabin 2 vaccine virus (cVDPV2) have been increasing in frequency. The current strategies for combating cVDPV2 involve supplemental immunization activities with monovalent Sabin 2 oral poliovirus (mOPV2), which can inadvertently seed future cVDPV2 outbreaks. Accurately assessing future cVDPV2 outbreak risk following mass mOPV2 campaigns is critical poliovirus eradication efforts but must consider the interaction between genetic reversion and epidemiological transmission. We developed an evolutionary epidemiology model to integrate Sabin 2 genetic reversion and transmission into a single framework to evaluate their relative contribution to cVDPV2 outbreaks and inform future intervention strategies.