Social immunity modulates competition between coinfecting pathogens

Coinfections with multiple pathogens can result in complex within‐host dynamics affecting virulence and transmission. While multiple infections are intensively studied in solitary hosts, it is so far unresolved how social host interactions interfere with pathogen competition, and if this depends on coinfection diversity. We studied how the collective disease defences of ants – their social immunity – influence pathogen competition in coinfections of same or different fungal pathogen species. Social immunity reduced virulence for all pathogen combinations, but interfered with spore production only in different‐species coinfections. Here, it decreased overall pathogen sporulation success while increasing co‐sporulation on individual cadavers and maintaining a higher pathogen diversity at the community level. Mathematical modelling revealed that host sanitary care alone can modulate competitive outcomes between pathogens, giving advantage to fast‐germinating, thus less grooming‐sensitive ones. Host social interactions can hence modulate infection dynamics in coinfected group members, thereby altering pathogen communities at the host level and population level.     

Immune responses against multiple epitopes: a theory for immunodominance and antigenic variation

A simple and natural model for the nonlinear interaction between the immune system and multiple epitopes of a genetically variable pathogen can explain the main features of the complex phenomenon of immunodominance. In this model, antigenically homogeneous populations of pathogens stimulate an immunodominant response against a single epitope. In contrast, a heterogeneous pathogen population induces a dynamically complicated array of fluctuating responses against multiple epitopes. Antigenic escape in one epitope can shift immunodominance to other, potentially weaker, epitopes, thereby altering the selective pressures on the pathogen population as a whole. These ideas are compared with detailed studies of the shifting patterns of antigenic variation and cytotoxic T-cell responses seen in HIV-1 infected patients.     

Expanding host specificity and pathogen sharing beyond viruses

Most emerging pathogens of humans can infect multiple host species (Woolhouse & Gowtage‐Sequeria, 2005). This simple fact has motivated multiple large‐scale, comparative analyses of the drivers of pathogen sharing and zoonotic pathogen richness among hosts as well as the factors determining the zoonotic potential of pathogens themselves. However, most of this work focuses on viruses, limiting a broader understanding of how host range varies within and between pathogen groups. In this issue of Molecular Ecology, Shaw et al. (2020) compile a comprehensive data set of host–pathogen associations across viruses and bacteria and test whether previous patterns observed in the former occur in the latter. They find most viruses and bacteria are specialists, and viruses are more likely to be generalists; however, generalist bacteria encompass multiple host orders, whereas viral sharing occurs more within host orders. Lastly, the authors demonstrate that many factors previously identified as predictors of zoonotic richness for viruses occur for bacteria and that host phylogenetic similarity is a primary determinant of cross‐species transmission. However, pathogen sharing with humans was more common and more weakly related to phylogenetic distance to Homo sapiens for bacteria compared to viruses, suggesting the former could pose greater spillover risks across host orders. This work represents a key advance in our understanding of host specificity and pathogen sharing beyond viruses.     

Pathogen relatedness affects the prevalence of within-host competition

Although the evolutionary consequences of within-host competition among pathogens have been examined extensively, there exists a critical gap in our understanding of factors determining the prevalence of multiple infections. Here we examine the effects of relatedness among strains of the anther-smut pathogen Microbotryum violaceum on the probability of multiple infection in its host, Silene latifolia, after sequential inoculations. We found a significantly higher probability of multiple infection when interacting strains were more closely related, suggesting mechanisms of competitive exclusion that are conditional on genotypic characteristics of the strains involved. Pathogen relatedness therefore determines the prevalence of multiple infection in addition to its outcome, with important consequences for our understanding of virulence evolution and pathogen population structure and diversity.     

Plant-parasite interactions: has the gene-for-gene model become outdated?

The detection of pathogens by plants is often described as a ‘gene-for-gene’ interaction.

However, recent work from several laboratories indicates that, in some instances, a single gene product in the plant can mediate the recognition of multiple pathogen signals, and that multiple plant genes are required for the recognition of, and response to, a single pathogen signal.     

Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host’s immune system influences the pathogen’s transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence–transmission trade-offs and evolution in vector-borne pathogen–host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the \({\mathcal {R}}_0\) maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen \({\mathcal {R}}_0\), but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways.     

Monte Carlo Simulation of Pathogen Behavior during the Sprout Production Process

Food-borne disease outbreaks linked to the consumption of raw sprouts have become a concern over the past decade. A Monte Carlo simulation model of the sprout production process was created to determine the most-effective points for pathogen control. Published literature was reviewed, and relevant data were compiled. Appropriate statistical distributions were determined and used to create the Monte Carlo model with Analytica software. Factors modeled included initial pathogen concentration and prevalence, seed disinfection effectiveness, and sampling of seeds prior to sprouting, sampling of irrigation water, or sampling of the finished product. Pathogen concentration and uniformity of seed contamination had a large effect on the fraction of contaminated batches predicted by the simulation. The model predicted that sprout sampling and irrigation water sampling at the end of the sprouting process would be more effective in pathogen detection than seed sampling prior to production. Day of sampling and type of sample (sprout or water) taken had a minimal effect on rate of detection. Seed disinfection reduced the proportion of contaminated batches, but in some cases it also reduced the ability to detect the pathogen when it was present, because cell numbers were reduced below the detection limit. Both the amount sampled and the pathogen detection limit were shown to be important variables in determining sampling effectiveness. This simulation can also be used to guide further research and compare the levels of effectiveness of different risk reduction strategies.     

Monte Carlo simulation of pathogen behavior during the sprout production process

Food-borne disease outbreaks linked to the consumption of raw sprouts have become a concern over the past decade. A Monte Carlo simulation model of the sprout production process was created to determine the most-effective points for pathogen control. Published literature was reviewed, and relevant data were compiled. Appropriate statistical distributions were determined and used to create the Monte Carlo model with Analytica software. Factors modeled included initial pathogen concentration and prevalence, seed disinfection effectiveness, and sampling of seeds prior to sprouting, sampling of irrigation water, or sampling of the finished product. Pathogen concentration and uniformity of seed contamination had a large effect on the fraction of contaminated batches predicted by the simulation. The model predicted that sprout sampling and irrigation water sampling at the end of the sprouting process would be more effective in pathogen detection than seed sampling prior to production. Day of sampling and type of sample (sprout or water) taken had a minimal effect on rate of detection. Seed disinfection reduced the proportion of contaminated batches, but in some cases it also reduced the ability to detect the pathogen when it was present, because cell numbers were reduced below the detection limit. Both the amount sampled and the pathogen detection limit were shown to be important variables in determining sampling effectiveness. This simulation can also be used to guide further research and compare the levels of effectiveness of different risk reduction strategies.     

The acquisition of hypovirulence in host-pathogen systems with three trophic levels

A major focus of research on the dynamics of host-pathogen interactions has been the evolution of pathogen virulence, which is defined as the loss in host fitness due to infection. It is usually assumed that changes in pathogen virulence are the result of selection to increase pathogen fitness. However, in some cases, pathogens have acquired hypovirulence by themselves becoming infected with hyperparasites. For example, the chestnut blight fungus Cryphonectria parasitica has become hypovirulent in some areas by acquiring a double-stranded RNA hyperparasite that debilitates the pathogen, thereby reducing its virulence to the host. In this article, we develop and analyze a mathematical model of the dynamics of host-pathogen interactions with three trophic levels. The system may be dominated by either uninfected (virulent) or hyperparasitized (hypovirulent) pathogens, or by a mixture of the two. Hypovirulence may allow some recovery of the host population, but it can also harm the host population if the hyperparasite moves the transmission rate of the pathogen closer to its evolutionarily stable strategy. In the latter case, the hyperparasite is effectively a mutualist of the pathogen. Selection among hyperparasites will often minimize the deleterious effects, or maximize the beneficial effects, of the hyperparasite on the pathogen. Increasing the frequency of multiple infections of the same host individual promotes the acquisition of hypovirulence by increasing the opportunity for horizontal transmission of the hyperparasite. This effect opposes the usual theoretical expectation that multiple infections promote the evolution of more virulent pathogens via selection for rapid growth within hosts.     

耳念珠菌的流行病学和生物学研究进展

耳念珠菌Candida auris已成为引起严重院里感染的新兴病原真菌。自2009年第一次报道以来,耳念珠菌在全球迅速传播并导致几次院内感染的暴发。与念珠菌属其他成员相比,耳念珠菌具有诸多特点,比如多重耐药、鉴别困难、死亡率高、易在医院内传播等。关于耳念珠菌的生物学和致病性研究越来越多,我们对耳念珠菌的认识也逐渐增强,本综述详细地介绍了耳念珠菌全球感染的流行病学以及该病原真菌的基本生物学特征,并对其毒力和耐药机制研究进展进行汇总,对未来关于耳念珠菌研究的前景进行了展望。     

The impact of non-lethal synergists on the population and evolutionary dynamics of host-pathogen interactions

Multiple pathogenic infections can influence disease transmission and virulence, and have important consequences for understanding the community ecology and epidemiology of host-pathogen interactions. Here the population and evolutionary dynamics of a host-pathogen interaction with free-living stages are explored in the presence of a non-lethal synergist that hosts must tolerate. Through the coupled effects on pathogen transmission, host mass gain and allometry it is shown how investing in tolerance to a non-lethal synergist can lead to a broad range of different population dynamics. The effects of the synergist on pathogen fitness are explored through a series of life-history trait trade-offs. Coupling trade-offs between pathogen yield and pathogen speed of kill and the presence of a synergist favour parasites that have faster speeds of kill. This evolutionary change in pathogen characteristics is predicted to lead to stable population dynamics. Evolutionary analysis of tolerance of the synergist (strength of synergy) and lethal pathogen yield show that decreasing tolerance allows alternative pathogen strategies to invade and replace extant strategies. This evolutionary change is likely to destabilise the host-pathogen interaction leading to population cycles. Correlated trait effects between speed of kill and tolerance (strength of synergy) show how these traits can interact to affect the potential for the coexistence of multiple pathogen strategies. Understanding the consequences of these evolutionary relationships is important for the both the evolutionary and population dynamics of host-pathogen interactions.     

The roles of pathogen small RNAs

Regulatory small RNAs (sRNAs), also known as non-coding RNA, are not translated into proteins and widespread in prokaryotes and eukaryotes. sRNAs involve in multiple fundamental cellular events. They are emerging regulatory elements that are gaining momentum. Knowledge of sRNA largely originates from eukaryotes. Prokaryotic sRNAs, particularly those of pathogen are only recently explored. The main types, function, and methodology to predict pathogen sRNAs are summarized in this review. Special focus is sRNAs regulating pathogen gene expression, particularly that of Mycobacterium tuberculosis, which is hitherto the most successful pathogen afflicting mankind.     

Dioecy,hermaphrodites and pathogen load in plants

Sex‐specific investment in pathogen resistance and immunity has been widely reported in animals and to a much lesser degree in plants. Here, we investigated the incidence of fungal pathogens in dioecious versus hermaphroditic plant species. We found that direct studies on differences between males and females in disease resistance or pathogen incidence were rare or non‐existent in plants, but if we made the prediction that if such differences exist (e.g. if males are less resistant than females), dioecious species should have a higher variation in pathogen diversity than hermaphrodites. Comparative studies on paired dioecious and hermaphrodite species from multiple plant families showed that hermaphrodites had a higher average pathogen load than dioecious species, consistent with the idea that higher outcrossing is beneficial to resistance to a greater diversity of pathogens. There was however no support for dioecious species also having a greater variance in pathogen diversity. Our results are consistent with dioecy providing a benefit in terms of pathogen resistance, but the data were insufficient to resolve if the male and female plants showed sex‐specific investment in resistance.     

Linking anthropogenic resources to wildlife–pathogen dynamics: a review and meta‐analysis

Urbanisation and agriculture cause declines for many wildlife, but some species benefit from novel resources, especially food, provided in human‐dominated habitats. Resulting shifts in wildlife ecology can alter infectious disease dynamics and create opportunities for cross‐species transmission, yet predicting host–pathogen responses to resource provisioning is challenging. Factors enhancing transmission, such as increased aggregation, could be offset by better host immunity due to improved nutrition. Here, we conduct a review and meta‐analysis to show that food provisioning results in highly heterogeneous infection outcomes that depend on pathogen type and anthropogenic food source. We also find empirical support for behavioural and immune mechanisms through which human‐provided resources alter host exposure and tolerance to pathogens. A review of recent theoretical models of resource provisioning and infection dynamics shows that changes in host contact rates and immunity produce strong non‐linear responses in pathogen invasion and prevalence. By integrating results of our meta‐analysis back into a theoretical framework, we find provisioning amplifies pathogen invasion under increased host aggregation and tolerance, but reduces transmission if provisioned food decreases dietary exposure to parasites. These results carry implications for wildlife disease management and highlight areas for future work, such as how resource shifts might affect virulence evolution.     

Virulence and community dynamics of fungal species with vertical and horizontal transmission on a plant with multiple infections

The virulence evolution of multiple infections of parasites from the same species has been modeled widely in evolution theory. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. Here, we characterized the virulence and community dynamics of fungal pathogens on the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was highly susceptible to diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The transmission mode mainly determined the pathogen community structure at the leaf spot level. Over time, the pathogen community within a leaf spot showed decreased Shannon diversity; moreover, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models for the virulence evolution of multiple infections are still valid in a complex realistic environment and highlight the impact of transmission mode on disease epidemics of foliar fungal pathogens. We also propose that seedborne fungi play an important role in structuring the foliar pathogen community from multiple infections within a leaf spot.     

Structural equation modelling analysis of evolutionary and ecological patterns in Australian Banksia

Evolutionary history of species, their geographic ranges, ecological ranges, genetic diversity, and resistance to pathogen infection, have been viewed as being mutually linked through a complex network of interactions. Previous studies have described simple correlations between pairs of these factors, while rarely separated the direct effects among multiple interacting factors. This study was to separate the effect of multiple interacting factors, to reveal the strength of the interactions among these factors, and to explore the mechanisms underlying the ecological and evolutionary processes shaping the geographic range, genetic diversity and fitness of species. I assembled comparative data on evolutionary history, geographic range, ecological range, genetic diversity, and resistance to pathogen infection for thirteen Banksia species from Australia. I used structural equation modelling to test multivariate hypotheses involving evolutionary history, geographic range, genetic diversity and fitness. Key results are: (1) Species with longer evolutionary times tend to occupy larger geographic ranges; (2) higher genetic diversity is directly associated with longer flowering duration in Banksia; and (3) species with higher genotypic diversity have higher level of resistance to infection caused by the pathogen Phytophthora cinnamomi, whereas heterozygosity has the opposite relationship with capacity of resistance to the infections caused by this pathogen. These results revealed a mutually linked and complex network of interactions among gene, species, environment and pathogen in evolutionary and ecological scales. These findings also have great practical significance and help to provide preemptive management options in pathogen control.     

临时多性伴接触者病原体感染分析

目的了解临时多性伴接触者病原体的感染情况。方法对2005年5月至2008年5月于我科门诊就诊的临时多性伴接触者进行病原体检测并分析病种特点。结果临时多性伴接触者病原体感染的阳性率为65．3％,2种以上病原体混合感染阳性率为31．4％,病原体以解脲脲原体为最高,人型支原体阳性率最低;病种以非淋菌性尿道炎、尖锐湿疣及梅毒为主。结论临时多性伴接触者容易感染病原体,混合性感染增多,病种以非淋菌性尿道炎、尖锐湿疣及梅毒为主。     

Selection of pathogen agents in weed biological control: critical issues and peculiarities in relation to arthropod agents

Abstract  Plant pathogens are playing an increasing role in classical biological control of weeds worldwide. This paper presents an explicit framework consisting of various interconnected steps to facilitate and streamline the selection process for pathogen agents. It also highlights and discusses critical issues associated with the various steps of the selection framework such as the climatic-matching approach to find well-adapted agents, host–pathogen matching and pathogen genetic structure. Processes and issues relating to the selection of pathogens are then contrasted with those usually adopted for arthropod selection in weed biological control. In both cases optimising the level of genetic diversity in introduced agents is seen as beneficial to biological control success. The difference in regulatory approach for multiple and genetically pure pathogen strains vs. genetically variable arthropod agents is highlighted for further scientific debate.