 The
Center for Microbial Pathogenesis is structured
to promote the collaboration of existing strengths
within the University in an effort to solve problems
in pathogenic microbiology. One of the obvious
juxtapositions of strengths is between those whose
primary interest is pathogenesis and those specializing
in microbial ecology. Powerful techniques to examine
the composition of and changes in microbial communities
in a variety of macroscopic and microscopic environments
have been developed by members of the MSU Center
for Microbial Ecology. Application of these techniques
to the study of infectious diseases is an exciting
new approach to the study of disease.
The
Center for Microbial Pathogenesis is applying
recent advances in molecular microbial ecology,
which to date have been used to study “traditional”
ecosystems, to problems in microbial infectious
diseases of plants and animals in order to better
understand and eventually control the fate of
pathogens, be it within the host or an alternate
reservoir. These advances include, most notably,
culture-independent molecular techniques to assess
microbial communities and the application of bioinformatics
derived data from genomic and proteomic analyses
to ecological questions. The CMP is employing
these techniques to determine the structure of
the ecosystem in which the pathogen must survive.
A microbial pathogen faces not only the host and
its immunological defense systems but also many
microbial populations that constitute “normal
flora”. Within a microbial community, populations
compete for ecosystem resources and thus the strategic
plan of a pathogen must include overcoming, evading,
or enlisting not only the host but also the indigenous
microbial populations that constitute normal flora.
This ecological perspective on pathogenesis includes
dissecting the complete ecosystem in each of our
research focus areas. Goals are to identify native
populations that interact with pathogens, either
synergistically or agonistically, and to use this
information as a basis for controlling pathogenesis.
There are two specific objectives to this approach:
- Define
the species composition of the normal community.
- Determine
how changes in the native community positively
or negatively influence the establishment of
a pathogen and how successful invasion affects
the native community structure.
 The
application of these molecular ecological approaches
to models of pathogenesis will establish the pathogen
in context with the complete ecosystem, not simply
the narrow perspective of “host-pathogen”
interactions. This broadened viewpoint should
provide additional tactics for the control of
pathogens. For example, the adaptive response
of the pathogen that may determine the success
of an infection could be regulated by the state
of surrounding microbial community. With this
basic premise in mind, the center is initially
focusing its effort on four complex ecosystems
amenable to these analyses. These are the human
vaginal tract, the gastrointestinal system of
mammals, the plant phyllosphere, and the mammalian
respiratory tract. Our approach for each system
is to ask the questions: What is the microbial
ecology of this system in health and in disease?
What is the composition of the microbial community
in health? How do shifts in the microbial community
affect the development of disease? What external
conditions affect the biodiversity and community
stability of the normal flora? Can probiotics
alter the microbial community in such a way as
to inhibit disease? These projects link pathogenesis
and microbial ecology, and are also tightly linked
to additional projects in the other thrust areas
of Genetic Adaptation of Pathogens, Common Virulence
Mechanisms of Pathogens, and Host Specificity.
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