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6 : Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host

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Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, Page 1 of 2

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Abstract:

This chapter focuses on the use of newer sequence-based methods for discovering novel microbial pathogens and some of the questions raised concerning interpretation of experimental findings. A remarkable degree of microbial diversity has recently emerged from surveys of natural environments that rely on direct acquisition and analysis of microbial gene sequences. Specialization and adaptation to an animal host are believed to involve acquisition of blocks of genes that encode virulence-associated attributes. The use of host markers to measure and predict host inflammation is not new. Two strategies are invoked by those who seek to identify novel or unrecognized microbial pathogens. The first is based on the straightforward notion that these pathogens will be found where there is unexplained disease, and in particular, disease that bears traditional features of infection. The second strategy is based on the observation that pathogens are often found within environmental niches that provide access to more privileged anatomic sites within a host. In addition to the distribution of microbial sequences and other signatures within the human body, the issue of kinetics must be confronted. With increasing experience comes appreciation of subtlety. This holds especially true for the use of microbial sequence-based detection methods. Broad-range ribosomal DNA (rDNA) polymerase chain reaction (PCR) frequently reveals bacterial sequences that are similar to but do not perfectly match any sequence in the available databases.

Citation: Relman D. 2000. Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, p 69-81. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch6
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Figures

Image of Figure 1.
Figure 1.

Evolutionary tree of the domain . The width and depth of each wedge are proportionate to the breadth and depth, respectively. of the diversity within its member. The wedges for divisions in which there are known cultivated members are black; those for divisions that comprise only sequences recovered directly from an environment are white. The seven divisions that contain members known to cause human disease are indicated by asterisks. Modified from reference with permission.

Citation: Relman D. 2000. Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, p 69-81. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch6
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Image of Figure 2.
Figure 2.

Sequential steps in any molecular approach to pathogen discovery.

Citation: Relman D. 2000. Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, p 69-81. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch6
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Image of Figure 3.
Figure 3.

Related questions pertaining to the selection of a sequence target for pathogen detection and characterization.

Citation: Relman D. 2000. Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, p 69-81. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch6
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Image of Figure 4.
Figure 4.

Molecular methods for pathogen discovery, organized according to source of the molecular signature.

Citation: Relman D. 2000. Sequence-Based Methods for Pathogen Discovery: the Complex Associations of Microbes, Microbial Sequences, and Host, p 69-81. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 4. ASM Press, Washington, DC. doi: 10.1128/9781555816971.ch6
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