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During the last decades of the 20 th century, the relation of man to microbial communities was reclaimed as symbiotic and integrated, not as inimical and antagonistic. As we have shown, context-sensitivity, immunopathology, discrepancy in virulence measurements, the limited applicability of Koch's postulates, in addition to the absence of definitive structural or functional differences between pathogen and commensal organisms, all support the view that a strict pathogen versus non-pathogen distinction, a legacy of the ontological model of disease, omits several relevant details involved in pathogenesis of most infectious pathologies.

Such a distinction becomes increasingly difficult to maintain as soon as we venture into a richer description of biological activities and processes and start to conceptualize microbes as evolving biological entities constantly interacting with their hosts. To address the theoretical challenges posed by the pathogen concept in post-genomic science, we have presented and discussed the implications of recent results from ecology and evolution that embrace the genetic diversity and underscore the relevance of microbial evolution.

We think that looking at pathogens as evolving ecological entities could lead to a more interactionist and systemic perspective on virulence and pathogenicity, and to a better understanding of the selective pressures favoring the transition from harmless commensals to infectious agents. Host and parasite genetics do matter, but classifying a microbe as a pathogen requires more than knowing its genome. The environment of the host and its history are key factors.

We argue that one possibility to clarify the debate is to focus on the virulence expressed by an infected host i. This does not solve the problem that there needs to be a threshold in switching from a quantitative trait virulence to a binary trait pathogenicity see Fig. Where to put the threshold is a decision that has to go beyond the scientific field for instance, as mentioned above, the existence or not of a cheap and efficient treatment should be a significant factor in deciding what the critical virulence is.

Host Parasite Relationship

At any rate, studying virulence forces us to acknowledge that hosts are not passive vehicles at the mercy of putative infectious germs but rather are themselves agents that take an active part, in several ways, in the processes of pathogenesis. Arguably, there is no single criterion of pathogenicity that adequately captures the mechanisms of pathogenesis. The binary conception according to which microorganisms are either one or the other is an abstraction from a more complex biological reality that ignores the facts that virulence is relatively transient, that commensals and parasites form a continuum, and that microorganisms constantly evolve.

The processual nature of pathogens is a compelling illustration of the recent argument to the effect that biological phenomena in health and disease may be better understood as forming a hierarchy of entangled processes, rather than a hierarchy of static things. Co-infection : Simultaneous infection of a host by more than one parasite strain or species.

Also referred to in the literature as multiple infection, mixed infection or polymicrobial infection. Ecological context : all the factors that are involved in the infectious process but beyond the control of the pathogen genotype itself, i. Note also that the notion of ecological context can be defined at the within-host level and, for a virus for instance, it could describe within-cell environments. Fitness : For a host, fitness is the ability to have many offspring. It has 2 components: host survival and host fecundity.

For a parasite, fitness is the ability to spread in the host population. GxGxE interaction : This notation summarizes the idea that a trait e. Of course, we could increase the number of G, for instance when we account for co-infections. Host-parasite interaction or infection : An interactive and dynamical biological system whose outcome is indeterminate and depends largely on the ecological context. Immunopathology : An outcome of host-parasite interactions, immunopathology describes a decrease in host fitness due to the immune response following infection. Opportunistic parasite : Parasite that cause virulent infections at higher rate in weakened hosts but are also able to cause disease in normal individuals, albeit less commonly so.

Parasite : any organism that decreases the fitness of its host by infecting it. This ecological definition includes both micro-parasites e. An infection in a given ecological context is either pathogenic or not. Resistance host : Ability of the host to prevent the infection or to decrease parasite load. This leads to a decrease in parasite fitness See also tolerance. Tolerance host : Ability of the host to decrease the virulence of an infection without affecting parasite load.

Contrary to resistance, tolerance increases the fitness of the parasite. This term can be defined in several ways. Evolutionary ecologists, for instance, define virulence as a quantitative trait that measures the decrease in host fitness due to an infection. We are grateful to Alex Powell for his linguistic help and to the 4 referees whose comments have greatly improved the paper.

National Center for Biotechnology Information , U. Journal List Virulence v. Published online Oct Author information Article notes Copyright and License information Disclaimer. The moral rights of the named author s have been asserted. This article has been cited by other articles in PMC. Abstract Until quite recently and since the late 19 th century, medical microbiology has been based on the assumption that some micro-organisms are pathogens and others are not.

Keywords: ecology, evolution, disease, infection, process, virulence. Open in a separate window. Pathogen in Post-Genomic Science Opportunities make pathogens Several pathogen-like organisms regularly colonize places in the human body and persist without causing clinical symptoms.

Immunopathology: when the enemy is us Parasites are not always solely to blame for the nature and scope of host damage: the immune system is often involved as well. Measuring and conceptualizing virulence Virulence is commonly thought of as a microbial property. Pathogens have no structure or function unique to them From the last 3 decades of the 19 th century until today several pathogen-like organisms have been classified on the basis of their physiological, morphological, cellular, and molecular traits.

Multiple infections and within-host diversity The implicit notion that a single germ is causally responsible for pathogenesis diverts from considering within- and between-host selection pressures, among other relevant factors shaping virulence. Microbial evolution Multiple infections and within-host diversity raise a related issue, namely microbial evolution. Conclusion During the last decades of the 20 th century, the relation of man to microbial communities was reclaimed as symbiotic and integrated, not as inimical and antagonistic.

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What is a pathogen? Toward a process view of host-parasite interactions

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The Problem with Virulence

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The Nature of Host Parasite Interactions

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