Ending the War Metaphor The Changing Agenda for Unraveling the Host-Microbe Relationship: Workshop Summary (2006) / Chapter Skim
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2 Beyond the Gut: Insights from Other Host-Microbe Systems
2 Beyond the Gut: Insights from Other Host-Microbe Systems
Pages 80-101
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From page 80... ...
The first paper is also coauthored by workshop presenter Jo Handelsman. Contending that the advancement of infectious disease research lies in understanding the nature of cooperation within microbial communities and its contribution to host health, the authors lead a guided tour of insights, derived from studies of plant pathology, that raise the possibility of harnessing the natural microbial communities of humans for disease prevention.
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From page 81... ...
The preponderance of conserved motifs and, presumably, mechanisms among plant and animal proteins involved with innate immunity has encouraged communication and even collaboration among the scientists who study these systems in widely different species -- an unfortunately rare occurrence that may yield significant insights on the structure, function, and evolution of innate immunity. IT TAKES A VILLAGE: ROLE OF INDIGENOUS MICROBIAL COMMUNITIES IN INFECTIOUS DISEASE Christina Matta and Jo Handelsman1 Summary The microbial communities that reside on and inside plants and animals are a key to host health.
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From page 82... ...
For both the plant sciences and biomedicine to benefit from each other's expertise, we need to rebuild the ties and foster collaboration between plant pathology and human infectious disease. Crossing the Disciplinary Divide: Microbiology in Historical Perspective The role plant sciences have played in shaping the content and methods of modern bacteriology has been overshadowed by the popular appeal of medical breakthroughs.
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From page 83... ...
As early as 1872, Cohn had presented strong evidence that bacteria cause disease when he published his observations of bacteria in diseased organisms and the loss of disease-causing ability when an infectious fluid was filtered. Moreover, Cohn's taxonomic and morphological study of bacteria provided the observations necessary to quell continuing debates about pleomorphism, a doctrine that posited that all bacteria were a single species and that the shape of a bacterium was either determined by the organism's stage in its life cycle or by environmental conditions (or some combination of both)
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From page 84... ...
had begun experimenting with obtaining pure cultures of pigmented bacteria as early as 1870. By the time Koch published his methods for studying pathogenic organisms in culture in 1881, then, methods for isolating individual organisms and reintroducing them to host tissue were widespread in mycology and already under development in bacteriology.
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From page 85... ...
The breakdown of this interdisciplinary exchange has led biomedical scientists to overlook recent breakthroughs in the plant sciences that might advance their own scientific progress. Trapping Promoters on Two Continents In 1988, for example, Michael Daniels' group at the John Innes Institute published their elegant method for isolating promoters from the plant pathogen Xanthomonas campestris, which involved cloning fragments of the X
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86 ENDING THE WAR METAPHOR FIGURE 2-2 Schematic depiction of the first strategies to select in vivo for promoters that are induced by plant (left panel) or animal (right panel)
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It is time to examine the role of the microbial communities that live on and in host plants and animals to identify factors that reduce the effectiveness of host-associated communities as barriers and that incite commensals in these communities to turn on their host and cause disease. Plant disease, more often than human disease, has been studied in a microbial context, so there is much to learn from plant pathology that may affect our understanding of pathogenesis in humans.
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From page 88... ...
. As the study of plant disease became more reductionist in the latter half of the 20th century, attention to microbial communities decreased and a causal relationship between the composition of the rhizosphere community and disease suppression was not established.
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From page 89... ...
The gut community, for example, may govern pathogen success by presenting a barrier to invasion that is predicated on the composition of the entire community, not one species. Alternatively, members of the natural community may potentiate the activity of the pathogen, facilitating infection or aggravating disease symptoms.
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. Similarly, it is such models that will furnish microbial ecology with the power to revolutionize approaches to avoiding, preventing, treating, and curing infectious disease of plants and animals.
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Plant pathology has addressed the role of microbial communities in plant disease, host genes that mediate resistance to disease, and environmental factors in development of disease epidemics. And as the United States confronts the potential for human epidemics derived from natural events or bioterrorism, we need to be equally cognizant of the vulnerability of our food supply to pathogens and microbial toxins.
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thaliana leads to rapid identification of components of host resistance and defense signaling pathways. Within each group, related bacterial, fungal, viral, and nematode pathogens cause diseases in both rice and Arabidopsis.
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In keeping with their lack of mobility, plants have very sophisticated ways of dealing with both biotic and abiotic stress. The plant's innate immune system employs hundreds of germline encoded pathogen receptors, most of which recognize type III effector proteins of bacterial pathogens.
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The bacterium delivers as many as 40 different effector proteins through the plant cell wall in order to suppress or modify the host plant's immune response and thereby permit colonization, much as effector proteins from animal pathogens do. A type III secretion system, essentially a molecular syringe, injects the bacterial effector proteins into the plant cell.
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However, a key finding from these studies is that resistance genes confer upon plant cells the ability to undergo programmed cell death upon recognizing a pathogen. By committing suicide, infected cells prevent the pathogen from spreading through the plant.
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Figure 2-6 shows similar motifs that occur in animal innate immune receptors and plant disease resistance proteins. For example, the Arabidopsis flagellin sensitivity 2 (FLS2)
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From page 97... ...
syringae effector protein called AvrRpt2. As shown in Figure 2-6, RPS2 is a membrane-associated NBS-LRR-type protein, with a coiled-coil "leucine zipper" nucleotide binding site at its N-terminus.
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. The bacterium delivers an inactive form of AvrRpt to the plant cell via a type III secretion system.
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A bioinformatics prediction has found putative AvrRpt2 cleavage sequences in approximately 20 proteins in the Arabidopsis genome, all of which are thus potential targets of that effector protein. By extension, it seems likely that among the 40 effector proteins produced by P
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2003. Genetic and molecular evidence that the Pseudomonas syringae type III effector protein AvrRpt2 is a cysteine protease.
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Presentation at the Fo rum on Microbial Threats Workshop Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship, Washington, D.C., Institute of Medicine, Forum on Microbial Threats. Waksman SA.
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