 What
genetic mechanisms permit pathogens to respond
to changing environments and to survive within
their hosts? - How
do pathogens regulate virulence?
- Can
inhibition of these regulatory processes prevent
or alter disease?
Description
Bacterial
pathogens, like all microbes, exist in complex
growth environments that expose the organism to
a variety of physical stresses and competing organisms.
Pathogens also encounter the harsh growth environment
and immune system of the host, which are specifically
designed to inhibit pathogen entry, survival,
and colonization. The appropriate coordination
of expression and activity of genes in bacterial
pathogens is essential for survival and disease
and directly depends on the ability of the pathogen
to rapidly sense and respond to a variety of environmental
cues. This well-coordinated regulatory network
provides a selective advantage to an organism
that is, at least initially, vastly outnumbered
by competitors.
 Regulation
of virulence factor production in prokaryotes
occurs at many levels from gene transcription
to protein secretion, and the study of these mechanisms
in a variety of pathogenic bacteria is a key research
area which will likely lead to new treatments
for infectious diseases. As a result of the selective
pressure of the host growth environment, bacterial
pathogens have evolved multiple mechanisms by
which they can sense and respond to their environments
including horizontal gene transfer between organisms
(to acquire new genes), genetic mutation and rearrangements
within a genome, and regulation of gene expression.
These mechanisms allow an organism to alter its
gene expression profile to promote its survival
in a given environment. While it is clear that
many organisms utilize these common strategies
to adapt to the host and environment, little is
understood about how this occurs in natural populations
in real ecological settings, how these strategies
evolved, and the short-term and long-term selective
advantages of these events to the pathogen as
well as the host.
One
goal of the Center for Microbial Pathogenesis
is to foster a multidisciplinary approach to understand
how microbial pathogens sense and respond to complex
growth environments. Specific research questions
that will be addressed are:
- What
communication takes place between incoming pathogens,
host cells, and resident microflora?
-
What are the mechanisms used by bacterial pathogens
to respond to environmental changes? Which genes
in a pathogen are modulated by communication
with the environment?
- How
do pathogens regulate virulence, and can inhibition
of these regulatory mechanisms inhibit or alter
the disease process?
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