Micro-evolution and emergence of pathogens

Changes in the epidemiology of infectious diseases are the direct result of ecological and evolutionary changes in hosts and parasites. Precisely what the causal processes are is rarely known in any particular case, and this hinders the design of appropriate control strategies. This is particularly so for emerging infections, as opportunity is rapidly lost to study the ecological parameters which might have affected initial emergence. However, molecular evolutionary studies of the pathogens can yield data which discriminate between possible causes. The current distribution of DNA sequence variation is important information which may reveal past and current changes in pathogen population structures, and can also identify adaptive changes in pathogen genes which have affected their evolution. Such studies have been quite intensively performed on particular viral and bacterial pathogens, and some of the successes of these are noted here. Approaches to understanding the recent evolution of eukaryotic pathogens are outlined, with particular reference to current problems of emerging zoonoses, and changes in virulence and drug resistance.     

Exclusion of generalist pathogens in multihost communities

Knowing how to control a pathogen that infects more than one host species is of increasing importance because the incidence of such infections grows with continuing environmental change. Of concern are infections transmitted from wildlife to humans or livestock. To determine which options are available to control a pathogen in these circumstances, we analyze the pathogen invasion matrix for the multihost susceptible-infected-susceptible model. We highlight the importance of both community structure and the column sum or row sum index, an indicator of both force of infection and community stability. We derive a set of guidelines for constructing culling strategies and suggest a hybrid strategy that has the advantages of both the bottom-up and the top-down approaches, which we study in some detail. The analysis holds for an arbitrary number of host species, enabling the analysis of large-scale ecological systems and systems with spatial dimensions. We test the robustness of our methods by making two changes in the structure of the underlying dynamic model, adding direct competition and introducing frequency-dependent infection transmission. In particular, we show that the introduction of an additional host can eliminate the pathogen rather than eliminate the resident host. The discussion is illustrated with a reference to bovine tuberculosis.     

Diffuse coevolution: constraints on a generalist parasite favor use of a dead-end host

Many evolutionary models and empirical studies of parasite-host interactions consider single species of parasites exploiting single host species. However, many parasites are generalists in that they parasitize more than one host species (often many more) and establish associations with other hosts that cannot be described as true parasitism. We identify such an association, explain how constraints may maintain it, and indicate why such diffuse interactions are deserving of attention. We describe the use of two closely related Sympetrum dragonfly species by larvae of the water mite Arrenurus planus Marshall. Adults of one dragonfly species are resistant whereas adults of the other species are almost wholly susceptible to A. planus . However, A. planus attaches as often to the resistant host as it does to the susceptible host species when relative abundance and seasonal timing of adult emergence of both species is considered. We present evidence that mites track the susceptible host and are most active early in the season, when early-emerging unsuitable hosts are also present. Thus, use of resistant hosts appears an unavoidable outcome of constraints promoting discovery and use of susceptible hosts. Such findings have implications for studies of local adaptation and host switching.     

On the coevolution of pathogen and host: II. Selfing hosts and haploid pathogens

The theory of discrete time coevolution is applied to the problem of maintenance of genetic polymorphism with selfing hosts and haploid pathogens. It is shown that the usual simplifying assumption, discrete synchroized generations with no intraspecific frequency-dependent selection, precludes stability. This situation is not corrected by the incorporation of special features such as mutation, alternate hosts, partial outcrossing of the hosts, or genetic recombination in the pathogen population.     

The coevolution of cooperation and dispersal in social groups and its implications for the emergence of multicellularity

Background  

Recent work on the complexity of life highlights the roles played by evolutionary forces at different levels of individuality. One of the central puzzles in explaining transitions in individuality for entities ranging from complex cells, to multicellular organisms and societies, is how different autonomous units relinquish control over their functions to others in the group. In addition to the necessity of reducing conflict over effecting specialized tasks, differentiating groups must control the exploitation of the commons, or else be out-competed by more fit groups.     

Multiple scales of selection influence the evolutionary emergence of novel pathogens

When pathogens encounter a novel environment, such as a new host species or treatment with an antimicrobial drug, their fitness may be reduced so that adaptation is necessary to avoid extinction. Evolutionary emergence is the process by which new pathogen strains arise in response to such selective pressures. Theoretical studies over the last decade have clarified some determinants of emergence risk, but have neglected the influence of fitness on evolutionary rates and have not accounted for the multiple scales at which pathogens must compete successfully. We present a cross-scale theory for evolutionary emergence, which embeds a mechanistic model of within-host selection into a stochastic model for emergence at the population scale. We explore how fitness landscapes at within-host and between-host scales can interact to influence the probability that a pathogen lineage will emerge successfully. Results show that positive correlations between fitnesses across scales can greatly facilitate emergence, while cross-scale conflicts in selection can lead to evolutionary dead ends. The local genotype space of the initial strain of a pathogen can have disproportionate influence on emergence probability. Our cross-scale model represents a step towards integrating laboratory experiments with field surveillance data to create a rational framework to assess emergence risk.     

Historic emergence, impact and current status of shrimp pathogens in the Americas

Shrimp farming in the Americas began to develop in the late 1970s into a significant industry. In its first decade of development, the technology used was simple and postlarvae (PLs) produced from wild adults and wild caught PLs were used for stocking farms. Prior to 1990, there were no World Animal Health Organization (OIE) listed diseases, but that changed rapidly commensurate with the phenomenal growth of the global shrimp farming industry. There was relatively little international trade of live or frozen commodity shrimp between Asia and the Americas in those early years, and with a few exceptions, most of the diseases known before 1980 were due to disease agents that were opportunistic or part of the shrimps' local environment. Tetrahedral baculovirosis, caused by Baculovirus penaei (BP), and necrotizing hepatopancreatitis (NHP) and its bacterial agent Hepatobacterium penaei, were among the "American" diseases that eventually became OIE listed and have not become established outside of the Americas. As the industry grew after 1980, a number of new diseases that soon became OIE listed, emerged in the Americas or were introduced from Asia. Spherical baculovirus, caused by MBV, although discovered in the Americas in imported live Penaeus monodon, was subsequently found to be common in wild and farmed Asian, Australian and African penaeids. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) was introduced from the Philippines in the mid 1970s with live P. monodon and was eventually found throughout the Americas and subsequently in much of the shrimp farming industry in the eastern hemisphere. Taura syndrome emerged in Penaeus vannamei farms in 1991-1992 in Ecuador and was transferred to SE Asia with live shrimp by 1999 where it also caused severe losses. White Spot Disease (WSD) caused by White spot syndrome virus (WSSV) emerged in East Asia in ～1992, and spread throughout most of the Asian shrimp farming industry by 1994. By 1995, WSSV reached the eastern USA via frozen commodity products and it reached the main shrimp farming countries of the Americas located on the Pacific side of the continents by the same mechanism in 1999. As is the case in Asia, WSD is the dominant disease problem of farmed shrimp in the Americas. The most recent disease to emerge in the Americas was infectious myonecrosis caused by IMN virus. As had happened before, within 3years of its discovery, the disease had been transferred to SE Asia with live P. vannamei, and because of its impact on the industry and potential for further spread in was listed by the OIE in 2005. Despite the huge negative impact of disease on the shrimp farming industry in the Americas, the industry has continued to grow and mature into a more sustainable industry. In marked contrast to 15-20years ago when PLs produced from wild adults and wild PLs were used to stock farms in the Americas, the industry now relies on domesticated lines of broodstock that have undergone selection for desirable characteristics including disease resistance.     

The presence of generalist plant pathogens might not explain the long-term coexistence of plant species

Pathogens have been shown to contribute to the possibility of coexistence of competing plant species by creating ecological distinction between the coexisting species. This coexistence promoting mechanism resembles intra-specific density dependence as found in Lotka-Volterra models. However, plant species adapt in their level of resistance against pathogen infection and this adaptation has been shown to be traded-off by a reduction in growth rate. A model is developed to show that taking into account the possible adaptation of plant species to increase their resistance against pathogen infection by generalist pathogens has consequences for the coexistence of the plant species. The results show that in systems where plants adapt to the pathogen infection, coexistence becomes impossible. The implication of this finding is that plant pathogens might contribute less to the coexistence of plant species than is commonly thought.     

Novel insights into the emergence of pathogens: the case of chestnut blight

Exotic, invasive pathogens have emerged repeatedly and continue to emerge to threaten the world’s forests. Ecosystem structure and function can be permanently changed when keystone tree species such as the American chestnut (Castanea dentata) are eliminated from a whole range by disease. The fungal ascomycete pathogen Cryphonectria parasitica is responsible for causing chestnut blight. Once the pathogen was introduced into the Eastern US, where chestnuts were predominant, chestnuts were all but eliminated. This pathogen is currently causing extensive damage in Europe. A study in this issue of Molecular Ecology sheds new light on the pattern and process of emergence of this devastating plant pathogen ( Dutech et al. 2012 ). The authors used microsatellite markers to investigate the evolutionary history of C. parasitica populations introduced into North America and Europe. To infer sources of migrants and the migration events, the authors included putative source populations endemic to China and Japan, inferred potentially unsampled populations and conducted a multivariate population genetic and complex ABC analysis. Cryphonectria parasitica emerges as an example of an introduced pathogen with limited genotypic diversity and some admixture in the invaded ranges, yet repeated invasions into different areas of Europe and the United States. This work sheds new light on the emergence of C. parasitica providing compelling evidence that this pathogen emerged by repeated migration and occasional admixture.     

Molecular mechanisms underlying the emergence of bacterial pathogens: an ecological perspective

The rapid emergence of new bacterial diseases negatively affects both human health and agricultural productivity. Although the molecular mechanisms underlying these disease emergences are shared between human‐ and plant‐pathogenic bacteria, not much effort has been made to date to understand disease emergences caused by plant‐pathogenic bacteria. In particular, there is a paucity of information in the literature on the role of environmental habitats in which plant‐pathogenic bacteria evolve and on the stress factors to which these microbes are unceasingly exposed. In this microreview, we focus on three molecular mechanisms underlying pathogenicity in bacteria, namely mutations, genomic rearrangements and the acquisition of new DNA sequences through horizontal gene transfer (HGT). We briefly discuss the role of these mechanisms in bacterial disease emergence and elucidate how the environment can influence the occurrence and regulation of these molecular mechanisms by directly impacting disease emergence. The understanding of such molecular evolutionary mechanisms and their environmental drivers will represent an important step towards predicting bacterial disease emergence and developing sustainable management strategies for crops.     

Historic emergence, impact and current status of shrimp pathogens in Asia

It is estimated that approximately 60% of disease losses in shrimp aquaculture have been caused by viral pathogens and 20% by bacterial pathogens. By comparison, losses to fungi and parasites have been relatively small. For bacterial pathogens, Vibrio species are the most important while for viral pathogens importance has changed since 2003 when domesticated and genetically selected stocks of the American whiteleg shrimp Penaeus (Litopenaeus) vannamei (Boone 1931) replaced the formerly dominant giant tiger or black tiger shrimp Penaeus (Penaeus) monodon (Fabricius 1798) as the dominant cultivated species. For both species, white spot syndrome virus (WSSV) and yellow head virus (YHV) are the most lethal. Next most important for P. vannamei is infectious myonecrosis virus (IMNV), originally reported from Brazil, but since 2006 from Indonesia where it was probably introduced by careless importation of shrimp aquaculture stocks. So far, IMNV has not been reported from other countries in Asia. Former impacts of Taura syndrome virus (TSV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) on this species have dramatically declined due to the introduction of tolerant stocks and to implementation of good biosecurity practices. Another problem recently reported for P. vannamei in Asia is abdominal segment deformity disease (ASDD), possibly caused by a previously unknown retrovirus-like agent. Next most important after WSSV and YHV for P. monodon is monodon slow growth syndrome (MSGS) for which component causes appear to be Laem Singh virus (LSNV) and a cryptic integrase containing element (ICE). Hepatopancreatic parvovirus (HPV) and monodon baculovirus (MBV) may be problematic when captured P. monodon are used to produce larvae, but only in the absence of proper preventative measures. Since 2009 increasing losses with P. vannamei in China, Vietnam and now Thailand are associated with acute hepatopancreatic necrosis syndrome (AHPNS) of presently unknown cause. Despite these problems, total production of cultivated penaeid shrimp from Asia will probably continue to rise as transient disease problems are solved and use of post larvae originating from domesticated SPF shrimp stocks in more biosecure settings expands.     

The effect of disease life history on the evolutionary emergence of novel pathogens

We present a general analytical result for the probability that a newly introduced pathogen will evolve adaptations that allow it to maintain itself within any novel host population, as a function of disease life-history parameters. We demonstrate that this probability of "evolutionary emergence" depends on two key properties of the disease life history: (i) the basic reproduction number and (ii) the expected duration of an infection. These parameters encapsulate all of the relevant information and can be combined in a very simple expression, with estimates for the rates of adaptive mutation, to predict the probability of emergence for any novel pathogen. In general, diseases that initially have a large reproductive number and/or that cause relatively long infections are the most prone to evolutionary adaptation.     

Molecular cloning and characterization of glucanase inhibitor proteins: coevolution of a counterdefense mechanism by plant pathogens

A characteristic plant response to microbial attack is the production of endo-beta-1,3-glucanases, which are thought to play an important role in plant defense, either directly, through the degradation of beta-1,3/1,6-glucans in the pathogen cell wall, or indirectly, by releasing oligosaccharide elicitors that induce additional plant defenses. We report the sequencing and characterization of a class of proteins, termed glucanase inhibitor proteins (GIPs), that are secreted by the oomycete Phytophthora sojae, a pathogen of soybean, and that specifically inhibit the endoglucanase activity of their plant host. GIPs are homologous with the trypsin class of Ser proteases but are proteolytically nonfunctional because one or more residues of the essential catalytic triad is absent. However, specific structural features are conserved that are characteristic of protein-protein interactions, suggesting a mechanism of action that has not been described previously in plant pathogen studies. We also report the identification of two soybean endoglucanases: EGaseA, which acts as a high-affinity ligand for GIP1; and EGaseB, with which GIP1 does not show any association. In vitro, GIP1 inhibits the EGaseA-mediated release of elicitor-active glucan oligosaccharides from P. sojae cell walls. Furthermore, GIPs and soybean endoglucanases interact in vivo during pathogenesis in soybean roots. GIPs represent a novel counterdefensive weapon used by plant pathogens to suppress a plant defense response and potentially function as important pathogenicity determinants.     

New aspects of staphylococcal infections: emergence of coagulase-negative staphylococci as pathogens

In contrast to the well-established pathogenStaphylococcus aureus, the coagulase-negative staphylococci, formerly collectively calledS. epidermidis, were until recently regarded as harmless commensals. During the last two decades, however, the coagulase-negative staphylococci have clearly emerged as pathogens in patients carrying artificial devices, such as prosthetic heart valves, hip prostheses and cerebrospinal fluid shunts, and in patients with compromised host defenses such as premature neonates and cancer and transplant patients. The present paper reviews current insights on classification, bacteriology, pathogenic potential and virulence factors of coagulase-negative staphylococci. In addition, the role of host defense factors in resistance to staphylococcal infection is summarized as well as the main features of the clinical syndromes in which coagulase-negative staphylococci are involved.     

Patterns of association between crucifers and their flower-mimic pathogens: host jumps are more common than coevolution or cospeciation

Morphological and molecular phylogenies of animal parasites have often shown parallel cladogenesis, supporting hypotheses of coevolution. Few studies of the phylogenetic history for plants and their pathogens exist. Gene-for-gene interactions suggest that plant pathogens ought to have similar phylogenetic histories as their hosts. However, high dispersability combined with an inability to choose to leave if an inappropriate host has been landed on could increase the likelihood of host jumps and thus decrease phylogenetic congruence between plant pathogens and their hosts. In this study, I examined the pattern of association between the flower-mimicking crucifer rusts and their hosts by comparing independent host phylogenies (based on both cpDNA trnL-F introns and nuclear internal transcribed spacer [ITS] sequences) with that of their rust pathogens (based on ITS sequences). The expectation was that if the pathogens coevolved or cospeciated with their hosts, then their phylogenies should be congruent. Host-tracking coevolution can be differentiated from cospeciation by examining the times of divergence: If the pathogens are younger than the hosts, then it is likely that host tracking has occurred. For the crucifer rusts and their hosts, there was little evidence of parallel cladogenesis, suggesting that both cospeciation and coevolutionary tracking are rare. Instead, the most common pattern was one of host jumps to geographically associated taxa. There are at least three factors that may have contributed to the geographic structuring of the data. First, along the east-west transect stretching from the Rocky Mountains to California, large differences in rainfall and the timing of rainfall may reduce long-distance gene flow. Second, although dispersal of infectious spores is by wind, sexual reproduction of these fungi depends on insects, which move short distances. Third, host shifts are most likely to occur to geographically available taxa. Any species that grows adjacent to infected plants will be exposed to millions of spores, and the probability of eventual infection by a new mutant increases with greater exposure. Thus, patterns of association between the crucifers and their flower-mimic pathogens reflect jumps to geographically available hosts, which are not necessarily those that are most closely related.     

On the coevolution of pathogen and host: I. General theory of discrete time coevolution

The theory of discrete time models of genetically conditioned coevolution is considered as an extension of classical population genetics theory. Strengths and weaknesses of the underlying assumptions are critically discussed in the context of host-pathogen interactions. Convenient formulae are provided to analyze the stability of equilibria. Some conclusions are drawn, which depend only on fairly general assumptions about the nature of host-pathogen coevolution.     

Making pathogens sociable: The emergence of high relatedness through limited host invasibility

Cooperation depends upon high relatedness, the high genetic similarity of interacting partners relative to the wider population. For pathogenic bacteria, which show diverse cooperative traits, the population processes that determine relatedness are poorly understood. Here, we explore whether within-host dynamics can produce high relatedness in the insect pathogen Bacillus thuringiensis. We study the effects of host/pathogen interactions on relatedness via a model of host invasion and fit parameters to competition experiments with marked strains. We show that invasibility is a key parameter for determining relatedness and experimentally demonstrate the emergence of high relatedness from well-mixed inocula. We find that a single infection cycle results in a bottleneck with a similar level of relatedness to those previously reported in the field. The bottlenecks that are a product of widespread barriers to infection can therefore produce the population structure required for the evolution of cooperative virulence.     

竞争进化与协同进化

竞争和协同作用是普遍存在于生物个体或种群之间的两种表现行为。大量实验和研究表明,竞争主导的生物进化是存在的,在一定范围和水平上竞争的结果有利于植物形态、生理适应特征及生活史适应策略的进化。协同能够使生物以最小的代价或成本实现自身在自然界的存在与繁殖(最大适合度);基于生态系统的稳定性和生物多样性的角度考虑,与竞争相辅相成、在一定条件下可以相互转化的协同作用更有利于生态系统各组分之间能量转化效率的提高,有利于加强系统自身的自组织能力,有利于维持生态系统的有序性和多样性。因此,协同作用的结果应该是更有利于生物进化,而且比竞争更普遍、更有意义。