Ending the War Metaphor The Changing Agenda for Unraveling the Host-Microbe Relationship: Workshop Summary (2006) / Chapter Skim
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5 Addressing Complexity in Microbial and Host Communities
5 Addressing Complexity in Microbial and Host Communities
Pages 175-206
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From page 175... ...
Stahl and coworkers demonstrate how links between human health status and oral microbiota composition can be explored with microarray-based tools that detect oral microorganisms and monitor their responses to environmental changes. In the near future, microarray-based diagnostics may allow dentists and clinicians to detect microbial sentinels of disease in the oral cavity, permitting earlier and more definitive diagnosis, as well as improved treatment.
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From page 176... ...
Woolhouse and coworker Sonya Gowtage-Sequeira present quantitative data on the diversity of human pathogens, investigate the association between emerging infectious diseases and host range, and examine the implications of having multiple hosts for pathogen evolution. Their findings reveal the importance of taking a broad, multidisciplinary, and ecological approach to the study of infectious disease rather than focusing on the interactions between individual host and microbe species.
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. More than 600 microbial species are known to inhabit the human oral cavity (Kolenbrander, 2000; Moore and Moore, 1994; Paster et al., 2001)
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in the local environment. Ultimately, associating these responses with disease development and progression is paramount to human oral cavity research.
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DNA microarrays, ordered displays of genetic material deposited on a surface or matrix, provide a highly parallel means for the analysis of genetic information. For instance, from hundreds to hundreds of thousands of ordered DNA oligonucleotide probes may be present on a single microarray.
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Studies with these arrays will undoubtedly lead to the discovery of novel diseasecausing attributes, identification of targets for novel therapeutics, and characterization of the genetic network that allows for biofilm formation on the hard and soft surfaces in the oral cavity. Another example of DNA microarrays is those composed of DNA oligonucleotide probes complementary to different regions of the rRNA molecules.
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Microarrays hold great promise for the analysis of oral cavity diseases, and with the continued evolution and improvement of the technology, dentists will be able to use these tools to better manage patients' health care. There are several advantages to the use of DNA microarrays in the dental setting.
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182 ENDING THE WAR METAPHOR FIGURE 5-2 Description of the MAGIChip DNA oligonucleotide microarray technology used in the Stahl laboratory.
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. To produce microarray-based in vitro diagnostic devices for clinical use, scientists must couple DNA microarray technology with microfluidics.
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They should be especially useful for the diagnosis of microbes in the oral cavity because they have a high probe density that allows for the simultaneous detection of multiple microbes. As the technology matures, pivotal issues in the sample collection and processing component of point-of-care microfluidic devices include: (1)
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As a step towards this goal, we present some quantitative data on numbers of human pathogens, investigate the association between emerging infectious diseases and host range, and briefly review the implications of having multiple hosts for pathogen evolution. The message to take will be that it is often insufficient to consider the interaction between a single host and a single pathogen in isolation.
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There are several published definitions of emerging or reemerging infectious diseases. The CDC suggest: "diseases of infectious origin whose incidence in humans has increased within the past two decades or threatens to TABLE 5-1 Counts of All, Emerging or Reemerging and Zoonotic Species of Human Pathogens and Comparison of the Relative Risks of Emergence for Zoonotic and Nonzoonotic Species for Each of the Major Pathogen Groups No.
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In other words, most human pathogens have a zoonotic component to their epidemiology. Secondly, the zoonotic fraction varies between the major pathogen groups; it is highest for the helminths, over 90 percent of which also infect other vertebrates.
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also noted that human pathogens were as likely to be associated with wildlife as they were with domestic animals, perhaps reflecting that emerging infectious diseases are often associated with human incursions into previously undeveloped regions. Species Jumps So far we have not distinguished between genuinely novel pathogens (emerging)
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Compatibility in turn reflects the pathogen's host range and the magnitude of any species barriers that inhibit transmission from one host species to another. The determinants of host range are, in general, quite poorly understood.
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Pathogens with high rates of genetic change are expected to be far more likely to establish themselves in the new host. This may explain or partly explain why singlestranded RNA viruses appear to be overrepresented among pathogens jumping into the human population: their mutation rate is orders of magnitude greater than that of most DNA-based pathogens.
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A single host species-humans -- has over 1,400 recognized pathogen species, over 12 percent of which are regarded as novel and/or causing increasing disease problems. Over half of all human pathogens, and three-quarters of emerging and reemerging pathogens, are shared with at least one other vertebrate host species.
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However, although zoonotic pathogens do represent the most likely source of emerging and reemerging infectious disease, only a small minority have proved capable of causing major epidemics in the human population. A recent, comprehensive literature survey of human pathogens listed >1,400 different species (Taylor et al., 2001)
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. Note that this definition includes pathogens for which humans are the main host and other vertebrates are only occasional hosts, as well as the opposite, but excludes purely human pathogens that recently evolved from nonhuman pathogens, e.g., HIV.
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and compared the ranking of drivers for the major pathogen groups and for zoonotic versus nonzoonotic pathogens. For the zoonotic species, we distinguished those known to be transmissible between humans, allowing that this might be through an indirect route (e.g., a vector or an intermediate host)
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Clear differences were found between the pathogen groups (24 = 154.3, p<<0.001) , with viruses greatly overrepresented among emerging and reemerging pathogens and helminths underrepresented.
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This corresponds to an RR of 2.0 and confirms the expectation that zoonotic pathogens are disproportionately likely to be associated with emerging and reemerging infectious diseases. This pattern varies somewhat across the different pathogen groups: for bacteria and fungi the association is strongest with RRs of 4.0 and 3.2, respectively; for viruses and protozoa, no obvious association was found, with RRs of 1.2 and 0.9, respectively; and for helminths (which are almost all zoonotic but very rarely emerging or reemerging)
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15 No 10 5 0 Ungulates Carnivores Rodents Nonmammals Primates Other Bats Mammals FIGURE 5-3 Numbers of species of zoonotic pathogens associated with different types of nonhuman host. Note that some pathogens are associated with >1 host.
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for which the host range is unknown are omitted. contaminated food and water and the lesser importance of international travel and changes in land use and agriculture for bacteria in comparison with viruses; and (3)
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. Second, emerging and reemerging pathogens are not strongly associated with particular nonhuman host types, although emerging and reemerging pathogens more often are those with broad host ranges that often encompass several mammalian orders and even nonmammals.
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Dr. Woolhouse is professor of infectious disease epidemiology in the Centre for Infectious Diseases at the University of Edinburgh.
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2003. The role of evolution in the emergence of infectious diseases.
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2003. Emerging Infectious Diseases.
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1994. The Evolution of Infectious Diseases.
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Emerging Infectious Diseases 1(1)
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2005. DNA microarrays as salivary diagnostic tools for characterizing the oral cavity's microbial commu nity.
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Presenta tion at the Forum on Microbial Threats Workshop Ending the War Metaphor: The Changing for Unraveling the Host-Microbe Relationship, Washington, D.C., Institute of Medicine, Forum on Microbial Threats. Woolhouse MEJ, Dye C
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