A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this (...) process remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole‐like structures of pathogens, thereby paving the way for the development of broadly effective anti‐microbial strategies for public health. (shrink)

Much research has explored behaviours that are linked with disgust sensitivity. Few studies, however, have been devoted to understanding how fixed or variable disgust sensitivity is. We therefore aimed to examine whether disgust sensitivity can change with the environment by repeatedly testing students whose environment was not changing as well as student cadets undergoing intensive training at an army camp. We found that an increase in the perceived harshness of the environment was associated with a decrease in pathogen disgust (...) sensitivity. Our results support the idea that disgust sensitivity is malleable depending on the environment. More specifically, we propose that in a harsh environment, where survival may be more difficult, pathogen disgust sensitivity may decrease to allow the consumption of available resources. (shrink)

It has been argued that people in areas with high pathogen loads will be more likely to avoid outsiders, to be biased in favor of in-groups, and to hold collectivist and conformist values. Cross-national studies have supported these predictions. In this paper we provide new pathogen codes for the 186 cultures of the Standard Cross-Cultural Sample and use them, together with existing pathogen and ethnographic data, to try to replicate these cross-national findings. In support of the theory, (...) we found that cultures in high pathogen areas were more likely to socialize children toward collectivist values (obedience rather than self-reliance). There was some evidence that pathogens were associated with reduced adult dispersal. However, we found no evidence of an association between pathogens and our measures of group bias (in-group loyalty and xenophobia) or intergroup contact. (shrink)

A novel class of proton‐ATPase has been identified in the vacuolar system of eukaryotic cells. The properties of these enzymes and their relation to other proton‐ATPases is discussed.

Within the same pathogen-stress framework as proposed by Fincher & Thornhill (F&T), we argue further that pathogen stress promotes matrilocal rather than patrilocal family ties which, in turn, slow down the process of modernity; and that pathogen stress promotes social learning or copying, including the adoption of foreign religions.

The development of technologies for the biopreservation of infectious organisms requires careful analysis of benefits and risks. This article reviews the regulatory landscape and oversight responsibilities in the United States in respect to pathogen biopreservation. Focused on two globally significant pathogens, Cryptosporidium and Plasmodium, the article explores advantages and potential risks of biopreservation concerning biosafety, biosecurity and biocontainment.

Skin-transmitted pathogens have threatened humans since ancient times. We investigated whether skin-transmitted pathogens were a subclass of disgust stimuli that evoked an emotional response that was related to, but distinct from, disgust and fear. We labelled this response “the heebie jeebies”. In Study 1, coding of 76 participants’ experiences of disgust, fear, and the heebie jeebies showed that the heebie jeebies was elicited by unique stimuli which produced skin-crawling sensations and an urge to protect the skin. In Experiment 2,350 participants’ (...) responses to skin-transmitted pathogen, fear-inducing, and disgust-inducing vignettes showed that the vignettes elicited sensations and urges which loaded onto heebie jeebies, fear, and disgust factors, respectively. Experiment 3 largely replicated findings from Experiment 2 using video stimuli. Results are consistent with the notion that skin-transmitted pathogens are a subclass of disgust stimuli which motivate behaviours that are functionally consistent with disgust yet qualitatively distinct. (shrink)

Archaea are microorganisms that are distinct from bacteria and eukaryotes. They are prevalent in extreme environments, and yet found in most ecosystems. They are a natural component of the microbiota of most, if not all, humans and other animals. Despite their ubiquity and close association with humans, animals and plants, no pathogenic archaea have been identified. Because no archaeal pathogens have yet been identified, there is a general assumption that archaeal pathogens do not exist. This review examines whether this is (...) a good assumption by investigating the potential for archaea to be or become pathogens. This is achieved by addressing: the diversity of archaea versus known pathogens, opportunities for archaea to demonstrate pathogenicity and be detected as pathogens, reports linking archaea with disease, and immune responses to archaea. In addition, molecular and genomic data are examined for the presence of systems utilised in pathogenesis. The view of this report is that, although archaea can presently be described as non‐pathogenic, they have the potential to be (discovered as) pathogens. The present optimistic view that there are no archaeal pathogens is tainted by a severe lack of relevant knowledge, which may have important consequences in the future. BioEssays 25:1119–1128, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Anthropologists have documented substantial cross-society variation in people’s willingness to treat strangers with impartial, universal norms versus favoring members of their local community. Researchers have proposed several adaptive accounts for these differences. One variant of the pathogen stress hypothesis predicts that people will be more likely to favor local in-group members when they are under greater infectious disease threat. The material security hypothesis instead proposes that institutions that permit people to meet their basic needs through impartial interactions with strangers (...) reinforce a tendency toward impartiality, whereas people lacking such institutions must rely on local community members to meet their basic needs. Some studies have examined these hypotheses using self-reported preferences, but not with behavioral measures. We conducted behavioral experiments in eight diverse societies that measure individuals’ willingness to favor in-group members by ignoring an impartial rule. Consistent with the material security hypothesis, members of societies enjoying better-quality government services and food security show a stronger preference for following an impartial rule over investing in their local in-group. Our data show no support for the pathogen stress hypothesis as applied to favoring in-groups and instead suggest that favoring in-group members more closely reflects a general adaptive fit with social institutions that have arisen in each society. (shrink)

Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy (...) Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, how to ensure quality of information and clinical service upon disclosure of results to this demographic and how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management. Trial registration number ISRCTN83772183. (shrink)

In contrast to the great majority of mycobacterial species that are harmless saprophytes, Mycobacterium tuberculosis and other closely related tubercle bacilli have evolved to be among the most important human and animal pathogens. The need to develop new strategies in the fight against tuberculosis (TB) and related diseases has fuelled research into the evolutionary success of the M. tuberculosis complex members. Amongst the various disciplines, genomics and functional genomics have been instrumental in improving our understanding of these organisms. In this (...) review we will present some of the recent key findings on molecular determinants of mycobacterial pathogenicity and attenuation, the evolution of M. tuberculosis, genome dynamics, antigen mining for improved diagnostic and subunit antigens, and finally the identification of novel drug targets. The genomics revolution has changed the landscape of TB research, and now underpins our renewed efforts to defeat this deadly pathogen. (shrink)

Disgust is reasoned to operate in conjunction with the immune system to help protect the body from illness. However, less is known about the factors that impact the degree to which individuals invest in pathogen avoidance (disgust) versus pathogen management (prophylactic immunological activity). Here, we examine the role that one’s control over pathogen contact plays in resolving such investment trade-offs, predicting that (a) those from low control environments will invest less in pathogen-avoidance strategies and (b) investment (...) in each of these two strategies will occur in a compensatory fashion (i.e. they will be traded off with one other). Across four studies, we found support for these predictions, using a variety of manipulations and measures. By providing novel insights into how one’s control over pathogen exposure influences disgust sensitivity and immune system activity, the current research poses an important contribution to the literature on disgust, pathogen avoidance, and the immune system. (shrink)

Intracellular NLR (Nucleotide‐binding domain and Leucine‐rich Repeat‐containing) receptors are sensitive monitors that detect pathogen invasion of both plant and animal cells. NLRs confer recognition of diverse molecules associated with pathogen invasion. NLRs must exhibit strict intramolecular controls to avoid harmful ectopic activation in the absence of pathogens. Recent discoveries have elucidated the assembly and structure of oligomeric NLR signalling complexes in animals, and provided insights into how these complexes act as scaffolds for signal transduction. In plants, recent advances (...) have provided novel insights into signalling‐competent NLRs, and into the myriad strategies that diverse plant NLRs use to recognise pathogens. Here, we review recent insights into the NLR biology of both animals and plants. By assessing commonalities and differences between kingdoms, we are able to develop a more complete understanding of NLR function. (shrink)

We question the plausibility of Fincher & Thornhill's (F&T's) argument that localised pathogen-host coevolution leads to out-groups having pathogens more damaging than those infecting one's own family or religious group.

One way to understand philosophy as a form of therapy is this: it involves a philosopher who is trying to cure himself. He has been drawn into a certain philosophical frame of mind—the ‘disease’—and has thus infected himself with this illness. Now he is sick and trying to employ philosophy to cure himself. So philosophy is both: the ailment and the cure. And the philosopher is all three: pathogenic agent, patient, and therapist.

The behavioral immune system (BIS) includes perceptual mechanisms for detecting cues of contamination. Former studies have indicated that moisture has a disgusting property. Therefore, moisture could be a target for detecting contamination cues by the BIS. We conducted two experiments to examine the psychophysical basis of moisture perception and clarify the relationship between the perception of moisture and the BIS. We assumed that the number of high luminance areas in a visual image provided optical information that would enable the visual (...) perception of moisture. In two experiments, we presented eight images of dough that contained different amounts of moisture as experimental stimuli. The amount of moisture shown in the images was increased in eight steps, from 28.6% to 42.9% of the total weight of the dough. In Experiment 1, the images were randomly presented on a computer display, and the participants (n = 22) were asked to rank the images in the order of the visually perceived moisture content. In Experiment 2, the participants (n = 15) completed pairwise comparisons based on the perceived moistness of the images. Furthermore, to examine the BIS responses, the participants rated the strength of disgust evoked by the stimuli, their motivation to avoid touching the stimuli, and the estimated magnitude of the risk of contamination by physical contact with the stimuli. The results indicated that the moisture content and the numbers of high luminance areas in the images accurately predicted the perception of moisture, suggesting that the detection of visual moisture was highly accurate, and the optical information served as an essential perceptual cue for detecting moisture. On the other hand, the BIS responses peaked in response to stimuli having approximately 33% to 39% moisture content. These results show that objects containing a moderate amount of moisture could be the target of visually detecting pathogens by the BIS. (shrink)

Previous studies of Zika virus (ZIKV) pathogenesis have focused primarily on virus‐driven pathology and neurotoxicity, as well as host‐related changes in cell proliferation, autophagy, immunity, and uterine function. It is now hypothesized that ZIKV pathogenesis arises instead as an (unintended) consequence of host innate immunity, specifically, as the side effect of an otherwise well‐functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post‐transcriptional RNA (...) editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. The authors collect and synthesize existing evidence of ZIKV‐mediated changes in the expression of adenosine deaminases acting on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for future research directions, including potential treatment strategies. (shrink)

The Covid-19 pandemic has demonstrated the potential of genomic technologies for the detection and surveillance of infectious diseases. Pathogen genomics is likely to play a major role in the future of research and clinical implementation of genomic technologies. However, unlike human genetics, the specific ethical and social challenges associated with the implementation of infectious disease genomics has received comparatively little attention. In this paper, we contribute to this literature, focusing on the potential consequences for individuals and communities of the (...) use of these technologies. We concentrate on areas of challenges related to privacy, stigma, discrimination and the return of results in the cases of the surveillance of known pathogens, metagenomics and host genomics. (shrink)

Despite the impressive technological advances in medicine many people feel worse rather than better after entering the medical care system. This article considers the pathogenic effect of physicians, in particular the problems of: 1) noxious communication, and 2) excessive evaluation and overinterpretation of test results.

In their paper “How Causal are Microbiomes? A Comparison with the Helicobacter pylori Explanation of Ulcers,” Lynch, Parke, and O’Malley successfully argue that certain causal attributions made to the microbiome have not satisfied Koch’s postulates nor the interventionist framework. However, their argument involves an implicit assumption that cases such as H. pylori are sufficiently similar to cases involving the microbiome, such that causal attributions to both should be evaluated according to the same causal framework. Our commentary targets this assumption. First, (...) we introduce the historical circumstances that led to the formulation of Koch’s postulates in order to differentiate the case of the microbiome from that of infectious bacteria. Then, we introduce the concept of the holobiont, the idea that hosts and their symbionts should be conceptualized as a metaphysical and biological unit. Finally, using the holobiont concept, we argue that Koch’s postulates and the interventionist framework are ill-equipped to handle the microbiome. We conclude by suggesting that a revision of what counts as microbiological causality within the holobiont is justified. (shrink)

Although Archaea inhabit the human body and possess some characteristics of pathogens, there is a notable lack of pathogenic archaeal species identified to date. We hypothesize that the scarcity of disease‐causing Archaea is due, in part, to mutually‐exclusive phage and virus populations infecting Bacteria and Archaea, coupled with an association of bacterial virulence factors with phages or mobile elements. The ability of bacterial phages to infect Bacteria and then use them as a vehicle to infect eukaryotes may be difficult for (...) archaeal viruses to evolve independently. Differences in extracellular structures between Bacteria and Archaea would make adsorption of bacterial phage particles onto Archaea (i.e. horizontal transfer of virulence) exceedingly hard. If phage and virus populations are indeed exclusive to their respective host Domains, this has important implications for both the evolution of pathogens and approaches to infectious disease control. (shrink)

This article examines the use of cinematic microanalysis to capture, decompose, and interpret mother–infant interaction in the decades following the Second World War. Focusing on the films and writings of Margaret Mead, Ray Birdwhistell, René Spitz, and Sylvia Brody, it examines the intellectual culture, and visual methodologies, that transformed ‘pathogenic’ mothering into an observable process. In turn, it argues that the significance assigned to the ‘small behaviours’ of mothers provided an epistemological foundation for the nascent discipline of infant psychiatry. This (...) research draws attention to two new areas of enquiry within the history of emotions and the history of psychiatry in the post-war period: preoccupation with emotional absence and affectlessness, and their personal and cultural meanings; and the empirical search for the origin point, and early chronology, of mental illness. (shrink)

A number of observations have led researchers to postulate that, despite being replication‐defective, human endogenous retroviruses (HERVs) may have retained the potential to cause or contribute to disease. However, mechanisms of HERV pathogenicity might differ substantially from those of modern infectious retroviruses or of the infectious precursors of HERVs. Therefore, novel pathways of HERV involvement in disease pathogenesis should be investigated. Recent technological advances in sequencing and bioinformatics are making this task increasingly feasible. The accumulating knowledge of HERV biology may (...) also facilitate the definition and general acceptance of criteria that establish HERV pathogenicity. Here, we explore possible mechanisms whereby HERVs may cause disease and examine the evidence that either has been or should be obtained in order to decisively address the pathogenic potential of HERVs. (shrink)

In March 2003, the world discovered, again, that I humanity's battle with infectious diseases continues. The twenty-first century began with infectious diseases, especially HIV/AIDS, being discussed as threats to human rights, economic development, and national security. Bioterrorism in the United States in October 2001 increased concerns about pathogenic microbes. The global outbreak of severe acute respiratory syndrome in the spring of 2003 kept the global infectious disease challenge at the forefront of world news for weeks. At its May 2003 annual (...) meeting, the World Health organization asserted that SARS is “the first severe infectious disease to emerge in the twenty-first century” and “poses a serious threat to global health security, the livelihood of populations, the functioning of health systems, and the stability and growth of economies.”. (shrink)

Scrapie and Creutzfeldt–Jakob disease (CJD) are caused by prions, which appear to be different from both viruses and viroids. Prions contain protein which is required for infectivity, but no nucleic acid has been found within them. Prion proteins are encoded by a cellular gene and not by a nucleic acid within the infectious prion particle. A cellular homologue of the prion protein has been IDentified. The role of this homologue in metabolism is unknown. Prion proteins, but not the cellular homologue, (...) aggregate into rod‐shaped particles that are histo‐chemically and ultrastructurally IDentical to amyloid. Extracellular collections of prion proteins form amyloid plaques in scrapie‐ and CJD‐infected rodent brains as well as CJD‐infected human brains. Within the plaques, prion proteins assemble to form amyloid filaments. Elucidating the molecular differences between the prion protein and its cellular homologue may be important in understanding the chemical structure and replication of prions. (shrink)

Many countries around the world embrace freedom and democracy as part of their political culture. However, culture is at least in part a human response to the ecological challenges that a society faces; hence, it should not be surprising that the degree to which societies regulate the level of individual freedom is related to environmental circumstances. Previous research suggests that levels of societal freedom across countries are systematically related to three types of ecological threats: prevalence of pathogens, climate challenges, and (...) natural disaster threat. Though their incidence overlaps, the literature has not yet provided a competitive test. Drawing upon the ecocultural framework, we tested five rival hypotheses, alternately focused on the above ecological factors and their interactions with economic wealth in explaining country variations in socio-political freedom. Focusing on data from 150 countries, we performed a series of linear mixed-effects regressions predicting freedom in the domains of politics, media, and economy. We found that countries with higher pathogen prevalence were more likely to suppress democracy and media freedom. Economic wealth, however, moderated the effect of pathogen prevalence on economic freedom, with the main effect being only found among wealthy countries, but not among poor countries. In contrast, natural disaster threat predicted political freedom and press freedom only among poor countries, consistent with the idea that disaster threat accompanied by poor resources promote socio-political freedom as a means of increasing collective survival. Throughout our analyses, we found no support for hypotheses based on climatic challenges. In addition, our multilevel approach revealed that country scores for socio-political freedom were highly clustered within world regions, accounting for substantial portions of variance. Overall, the present research offers a nuanced view of the interplay between ecology and wealth in the emergence of socio-political freedom. We discuss new directions in future research considering methodological and theoretical contributions of the present findings. (shrink)

Breast cancer screening aims to help women by early identification and treatment of cancers that might otherwise be life-threatening. However, breast cancer screening also leads to the detection of some cancers that, if left undetected and untreated, would not have damaged the health of the women concerned. At the time of diagnosis, harmless cancers cannot be identified as non-threatening, therefore women are offered invasive breast cancer treatment. This phenomenon of identifying non-harmful cancers is called overdiagnosis. Overdiagnosis is morally problematic as (...) it leads to overall patient harm rather than benefit. Further, breast cancer screening is offered in a context that exaggerates cancer risk and screening benefit, minimises risk of harm and impedes informed choice. These factors combine to create pathogenic vulnerability. That is, breast cancer screening exacerbates rather than reduces women’s vulnerability and undermines women’s agency. This paper provides an original way of conceptualising agency-supporting responses to the harms of breast cancer overdiagnosis through application of the concept of pathogenic vulnerability. (shrink)

The emergence of the 2009 H1N1 virus pandemic was unexpected, since it had been predicted that the next pandemic would be caused by subtype H5N1. We also had to learn that a pandemic does not necessarily require the introduction of a new virus subtype into the human population, but that it may result from antigenic shift within the same subtype. The new variant was derived from human and animal viruses by genetic reassortment in the pig, supporting the concept that this (...) animal is the mixing vessel for the generation of new human influenza viruses. Although it is generally believed that the 2009 outbreak was mild, there have been severe cases particularly among the young and the middle‐aged. Pathogenicity and host range are determined to a large extent by the polymerase, the haemagglutinin and the NS1 protein of influenza A viruses. There is evidence that mutations of these proteins may change the pathogenicity of the new virus. (shrink)

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover (...) the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. (shrink)

By the end of the 1820s, an innovative product was introduced in the northern Italian editorial market: technical and popular periodicals offering “useful knowledge” to a larger audience composed of members of the provincial middle-class, clergymen, and modestly educated craftsmen. By examining their medical content, this paper shows that popularisation did not merely entail disseminating a set of stable, unanimous, and trustworthy medical doctrines; rather, it represented a crucial step in the making of science during a period in which medical (...) theories were still various and contradictory. Moreover, it demonstrates that the environmental and preventative approach to disease, which these medical contributors often employed, did reflect recent developments in chemical or physical knowledge and responded to pedagogical and informative goals; but it mostly served to affirm the social usefulness of medicine and the legitimacy of health professionals' participation in determining how to regulate more general epidemiologic, social, and political issues. (shrink)

The paper addresses some rhetorical uses of the figure of water management from the perspective of an affirmative approach to contamination which Derrida saw as constitutive of affirmation itself. Contaminated water and its discontents discussed in the text frequently appears in various kinds of writings as a frightening figure of contamination which simultaneously brings in the figure of water management as a way of controlling the purity of cultural exchanges and transmissions in which, as Caroline Petronius puts it, contagion journeys (...) out of medicine into culture. The paper also addresses water and its management from the perspective of Astrida Neimanis’s liquidizing of the border between the solid and the fluid as a border between the human and the inhuman. This perspective opens up the sphere of mutual contamination of the human and the inhuman and translates posthumanist theoretical positions into spheres of affirmative exchanges managed not by masters, but by Donna Haraway’s companion species whom, or which, we all are. (shrink)

The emergence of new techniques in both microbial biotechnology and artificial intelligence (AI) is opening up a completely new field for monitoring and sometimes even controlling the evolution of pathogens. However, the now famous generative AI extracts and reorganizes prior knowledge from large datasets, making it poorly suited to making predictions in an unreliable future. In contrast, an unfamiliar perspective can help us identify key issues related to the emergence of new technologies, such as those arising from synthetic biology, whilst (...) revisiting old views of AI or including generative AI as a generator of abduction as a resource. This could enable us to identify dangerous situations that are bound to emerge in the not-too-distant future, and prepare ourselves to anticipate when and where they will occur. Here, we emphasize the fact that amongst the many causes of pathogen outbreaks, often driven by the explosion of the human population, laboratory accidents are a major cause of epidemics. This review, limited to animal pathogens, concludes with a discussion of potential epidemic origins based on unusual organisms or associations of organisms that have rarely been highlighted or studied. (shrink)

Although the type‐I interferon (IFN‐I) response is considered vertebrate‐specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN‐I response is induced by viruses and other intracellular pathogens and promotes resistance against infection. Whether the IPR and the IFN‐I response evolved in (...) a divergent or convergent manner is an unanswered and exciting question, which could be addressed by further studies of immunity against intracellular pathogens in C. elegans and other simple host organisms. Here we highlight similar roles played by RIG‐I‐like receptors, purine metabolism enzymes, proteotoxic stressors, and transcription factors to induce the IPR and IFN‐I response, as well as the similar consequences of these defense programs on organismal development. (shrink)

Genetic resources are a key resource for much biomedical research. Pathogenic genetic resources are of value in the identification, surveillance, understanding, and development of vaccines, treatments, and other responses to major public threats such as pandemic influenza outbreaks. Significant attempts have been made to improve the international governance of infectious disease over the last decade, but the handling of pathogenic genetic resources remains contentious and problematic. The need to address the deficiencies in current arrangements (e.g., the World Health Organization's Pandemic (...) Influenza Preparedness Framework) is urgent because future outbreaks are likely to revert to the past situation in which developed states secured vaccine supplies for their own populations while leaving developing countries vulnerable to the pandemic. Thereby, the collaboration of developed countries with vital international systems such as the Global Influenza Surveillance and Response System is disincentivized. The current international approach to pathogenic genetic resources is based on the sovereign rights of states and access and benefit-sharing arrangements that stem from those rights. While this approach is consistent with international rules on other types of genetic resources, herein I argue that this is an inappropriate approach to pathogens on both political (serving public health goals) and ethical grounds (e.g., equity and justice). Instead I argue for a (modified) common heritage approach to pathogenic genetic resources, based on their intrinsic qualities (e.g., rapid mutation, easy transmissibility) and their value to global efforts to respond to disease outbreaks. I will further argue for de-linking access to these resources from benefit-sharing requirements; explaining that while there are strong justifications for both, their linkage (particularly for pathogenic genetic resources) is problematic and detrimental to the achievement of its intended goals (i.e., ensuring equitable benefit-sharing in return for access being granted). (shrink)

In fungi, cell fusion between genetically unlike individuals triggers a cell death reaction known as the incompatibility reaction. In Podospora anserina, the genes controlling this process belong to a gene family encoding STAND proteins with an N‐terminal cell death effector domain, a central NACHT domain and a C‐terminal WD‐repeat domain. These incompatibility genes are extremely polymorphic, subject to positive Darwinian selection and display a remarkable genetic plasticity allowing for constant diversification of the WD‐repeat domain responsible for recognition of non‐self. Remarkably, (...) the architecture of these proteins is related to pathogen‐recognition receptors ensuring innate immunity in plants and animals. Here, we hypothesize that these P. anserina incompatibility genes could be components of a yet‐unidentified innate immune system of fungi. As already proposed in the case of plant hybrid necrosis or graft rejection in mammals, incompatibility could be a by‐product of pathogen‐driven divergence in host defense genes. (shrink)

It is well known that microbial pathogens are able to subvert the host immune system in order to increase microbial replication and propagation. Recent research indicates that another arm of the immune response, that of the chemokine system, is also subject to this sabotage, and is undermined by a range of microbial pathogens, including viruses, bacteria, and parasites. Currently, it is known that the chemokine system is being challenged by a number of mechanisms, and still more are likely to be (...) discovered with further research. Here we first review the general mechanisms by which microbial pathogens bypass mammalian chemokine defences. Broadly, these can be grouped as viral chemokine interacting proteins, microbial manipulation of host chemokine and chemokine receptor expression, microbial blockade of host chemokine receptor signalling, and the largely hypothetical mechanisms of microbial enhancement of host anti‐chemokine networks (including digestion, antagonism, and neutralisation of host chemokines and chemokine receptors). We then discuss the potential results of these interactions in terms of outcome of infection. BioEssays 25:478–488, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Successful therapies to combat microbial diseases and cancers require incorporating ecological and evolutionary principles. Drawing upon the fields of ecology and evolutionary biology, we present a systems‐based approach in which host and disease‐causing factors are considered as part of a complex network of interactions, analogous to studies of “classical” ecosystems. Centering this approach around empirical examples of disease treatment, we present evidence that successful therapies invariably engage multiple interactions with other components of the host ecosystem. Many of these factors interact (...) nonlinearly to yield synergistic benefits and curative outcomes. We argue that these synergies and nonlinear feedbacks must be leveraged to improve the study of pathogenesis in situ and to develop more effective therapies. An eco‐evolutionary systems perspective has surprising and important consequences, and we use it to articulate areas of high research priority for improving treatment strategies. (shrink)