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Complex host-pathogen coevolution in the Apterostigma fungus-growing ant-microbe symbiosis.

BACKGROUND: The fungus-growing ant-microbe symbiosis consists of coevolving microbial mutualists and pathogens. The diverse fungal lineages that these ants cultivate are attacked by parasitic microfungi of the genus Escovopsis. Previous molecular analyses have demonstrated strong phylogenetic congruence between the ants, the ants-cultivated fungi and the garden pathogen Escovopsis at ancient phylogenetic levels, suggesting coevolution of these symbionts. However, few studies have explored cophylogenetic patterns between these symbionts at the recent phylogenetic levels necessary to address whether these parasites are occasionally switching to novel hosts or whether they are diversifying with their hosts as a consequence of long-term host fidelity. RESULTS: Here, a more extensive phylogenetic analysis of Escovopsis lineages infecting the gardens of Apterostigma ants demonstrates that these pathogens display patterns of phylogenetic congruence with their fungal hosts. Particular clades of Escovopsis track particular clades of cultivated fungi, and closely-related Escovopsis generally infect closely-related hosts. Discordance between host and parasite phylogenies, however, provides the first evidence for occasional host-switches or acquisitions of novel infections from the environment. CONCLUSION: The fungus-growing ant-microbe association has a complex coevolutionary history. Though there is clear evidence of host-specificity on the part of diverse Escovopsis lineages, these pathogens have switched occasionally to novel host fungi. Such switching is likely to have profound effects on how these host and parasites adapt to one another over evolutionary time scales and may impact how disease spreads over ecological time scales.

Agaricales↗

Entomopathogens: ecological manipulation of natural associations.

The control of insect pests with entomopathogens is unique, in that naturally occurring host-pathogen relations are manipulated to the benefit of man: protecting agricultural crops and forests or controlling insect vectors of disease. The isolation and identification of a virulent pathogen is the initial step in the development of a potential control agent. Production of the pathogen in adequate quantities must be possible either in vivo (insects) or in vitro (artificial medium). To insure usefulness, the pathogen must remain viable in the formulated form and after application in the field. Since inactivation rather than persistence is a problem, the pathogens must be formulated, protected, and applied to insure satisfactory pest control action. Studying the natural host--pathogen interactions will be necessary in order to manipulate the pathogen effectively, by introducing it at the most opportune time in the life cycle of the target pest. Generally, insect pathogens are more selective than conventional pesticides; this will limit their use and industrial development. Development, at least in part, by the public sector may be necessary and desirable. The most promising areas for the use of pathogens are in integrated pest management and in situations where pests have developed resistance to chemical control.

Animals↗

Ancient host-pathogen associations maintained by specificity of chemotaxis and antibiosis.

Switching by parasites to novel hosts has profound effects on ecological and evolutionary disease dynamics. Switching requires that parasites are able to establish contact with novel hosts and to overcome host defenses. For most host-parasite associations, it is unclear as to what specific mechanisms prevent infection of novel hosts. Here, we show that parasitic fungal species in the genus Escovopsis, which attack and consume the fungi cultivated by fungus-growing ants, are attracted to their hosts via chemotaxis. This response is host-specific: Escovopsis spp. grow towards their natural host cultivars more rapidly than towards other closely related fungi. Moreover, the cultivated fungi secrete compounds that can suppress Escovopsis growth. These antibiotic defenses are likewise specific: in most interactions, cultivars can inhibit growth of Escovopsis spp. not known to infect them in nature but cannot inhibit isolates of their naturally infecting pathogens. Cases in which cultivars are susceptible to novel Escovopsis are limited to a narrow set of host-parasite strain combinations. Targeted chemotactic and antibiotic responses therefore explain why Escovopsis pathogens do not readily switch to novel hosts, consequently constraining long-term dynamics of host-parasite coevolution within this ancient association.

Animals↗

Differential regulation of IL-12 and IL-10 gene expression in macrophages by the basic leucine zipper transcription factor c-Maf fibrosarcoma.

IL-12 is a principal activator of both innate and adaptive immunity against infectious agents and malignancies. Regulation of proinflammatory IL-12 gene expression in phagocytes by the anti-inflammatory cytokine IL-10 represents a major homeostatic process underlying host-pathogen and host-self interactions. Delineation of the signaling pathway of IL-10 is crucial to the understanding of immunological regulatory networks. In this study, we report that IL-10 and c-musculoaponeurotic fibrosarcoma (Maf) induce their mutual expression in inflammatory macrophages. We demonstrate that c-Maf is one of the physiological mediators of IL-10's immunosuppressive activities. When overexpressed, c-Maf selectively inhibits transcriptional activation of IL-12 p40 and p35 genes while potently activating IL-10 and IL-4 expression, potentially contributing to the development of a state of anti-inflammation and dichotomy of immunologic polarization. c-Maf induces changes in nuclear DNA-binding activities at multiple sites including the ets, GA-12, NF-kappaB, C/EBP, and AP-1 elements. Nonetheless, the essential c-Maf-responsive element appears to be located elsewhere. Inhibition of IL-12 p40 gene expression by c-Maf requires the N-terminal transactivation domain, suggesting an indirect mechanism of transcriptional inhibition involving the induction of an unidentified repressor. In c-Maf-deficient murine macrophages, IL-10 production is impaired. However, IL-10-mediated inhibition of IL-12 production remains intact, indicating the existence of alternative mediators in the absence of c-Maf, consistent with the observation that a functional AP-1 is required for this pathway.

Animals↗

Virulence testing of Listeria monocytogenes.

A major problem in understanding foodborne listeriosis from both the basic science and regulatory perspectives revolves around the role played by virulence factors of Listeria monocytogenes and how these interact with host susceptibility to result in the observed incidence of disease. From a mechanistic perspective, this problem has been well investigated, and many virulence components of L. monocytogenes have been discovered. Deletion of these genes results in large reductions in virulence functions in vitro and in vivo. The clonal bacteria and genetically identical hosts necessary to solve the riddles associated with virulence mechanisms are not likely to reflect the natural diversity found among wild populations of L. monocytogenes, including those associated with food. These factors contribute to a major dilemma in risk assessment and risk management of foodborne listeriosis: Although low-level L. monocytogenes contamination of certain foods is relatively common, suggesting widespread exposure, illness is overwhelmingly associated with only a relatively small subpopulation (3 of the 13 L. monocytogenes serotypes) and occurs in only a small proportion of susceptible individuals. Virulence testing based on DNA probes for virulence genes is confounded by the widespread distribution of these genes in food isolates. In terms of the distribution of virulence factors among food isolates of L. monocytogenes, only listeriolysin is well characterized, because beta-hemolysis is often used to confirm the presence of L. monocytogenes in foods. The presence of other virulence genes such as those involved in host cell invasion and cell-to-cell spread (inlA and actA) among food isolates has not been extensively investigated. How the presence of these components translates into functional virulence as measured in vivo and in vitro is also unknown. Animal studies and cell culture systems show a range of virulence among food isolates of L. monocytogenes. However, clinical isolates included in such studies are not consistently more virulent than food isolates with no known human disease association. Where multiple serotypes or ribotypes are compared, it has been difficult to demonstrate a consistent pattern of increased virulence associated with any subtype(s) in animal or in vitro studies. Development of model systems that adequately reflect the complexity of the host-pathogen relationship remains a challenge.

Animals↗

How reliable are models for malaria vaccine development? Lessons from irradiated sporozoite immunizations.

Models occupy a key position in the development of anti-parasitic vaccines, yet their relevance has been seldom addressed. It is customary to admit that malaria vaccine development requires easy-to-handle, laboratory models. Animal models involving predominantly inbred rodents and primates as parasite hosts are currently the basic tools for the study of host-parasite interactions. Literature however indicates that the induction of host protection is more difficult in natural host-parasite pairs than in experimental models of parasite infection. Moreover different models delineate a wide range of host-pathogen relationship profiles providing a mosaic of contradictory informations, yet there is little incentive to delineate their relevance or to exploit recent advances to develop improved model systems. In this context the analysis of natural host-parasite interactions between Plasmodium berghei and its mammalian host and reservoir, the tree rat Grammomys surdaster could ge of relevance in the study of host-parasite interactions.

Animals↗