The interactions that occur between microbes within the human body are central
to both health and disease. For example, many illnesses, such as respiratory
infections, gastroenteritis and periodontal diseases, often involve multiple
microorganisms. Microbe-microbe interactions can involve either, or both, antagonistic
or synergistic interactions, and the study of microbe-microbe interactions
is required in order to understand the in vivo activities of both pathogenic
and commensal microorganisms.
Our research also illustrates that many of the interactions between microbes
involve factors that are important for a microbe’s ability to cause disease
in humans. Thus, we can use microbe-microbe interaction systems to better understand
the molecular mechanisms that underlie different aspects of the host-pathogen
relationship.
Much of our work focuses on Pseudomonas aeruginosa and Candida albicans, two
important opportunistic human pathogens.
Click on the links below to read more about our work:
Bacterial-fungal interactions
Using tractable bacterial-fungal model systems with the bacterium Pseudomonas
aeruginosa and the fungus Candida albicans, we have uncovered multiple ways
in which these organisms alter the growth and behavior of each other.
Our
goals are:
- To understand the mechanisms by which microbes change their behavior
in the context of microbial communities and to determine how these changes
affect their interactions with the human host
- To examine microbial interactions as a way to gain insight into novel
ways to control microbial pathogens
- To develop new ways to study microbe-microbe interactions
We have found that C. albicans morphology is altered by a P. aeruginosa-produced
signaling molecule that accumulates to high levels in biofilms or colonies.
The mechanism by which the bacterial molecule affects C. albicans seems to
be similar to the C. albicans response to its own signaling molecule, farnesol
(Davis-Hanna et al., 2008). We have found that these molecules act by inhibiting
the conserved Ras1-adenylate cyclase-PKA-dependent pathway that controls
hyphal growth. Current work focuses on uncovering the mechanism by which
extracellular molecules modulate morphology and other cAMP-controlled processes
such as survival and nutrient acquisition. We are also pursuing an understanding
of the importance of these signals within microbial populations and communities.
C. albicans-produced farnesol alters P. aeruginosa virulence factor production
(Cugini et al., 2007). Furthermore, the fungus induces a change in the spectrum
of secreted virulence factors. We have found that a potent toxin, derived
from P. aeruginosa-produced phenazines localizes within fungal cells (Gibson
et al. 2009). We continue to characterize these molecular interactions to
identify new antifungal strategies and to better mixed species infections
(Left) A red pigmented phenazine derivative accumulates within fungal cells upon
co-culture with P. aeruginosa and kills the fungus (Gibson et al. 2009.). (Right)
Some strains exhibit altered responses to fungi.
Pseudomonas aeruginosa is both a common environmental bacterium and an important
opportunistic pathogen that is capable of causing a variety of severe infections.
This bacterium causes particularly devastating infections in the lungs of individuals
with diseases such as Cystic Fibrosis and chronic obstructive pulmonary disease.
P. aeruginosa secretes a phospholipase C that negatively impacts lung function.
The action of this enzyme leads to the release of choline containing products
that alters P. aeruginosa virulence-related characteristics in a variety of
ways.
Our goals are:
- To understand the regulation of phospholipase C (PlcH) production in vivo
and to understand the role of PlcH in P. aeruginosa-host interactions
- To analyze the effects of choline, a product of PlcH-mediated degradation
of PC on P. aeruginosa virulence-related traits
We have identified a positive regulatory loop for the induction of plcH controlled
by the transcription factor GbdR (Wargo et al. 2007, 2009). A combination of
genetic screens, mutant analysis and microarray studies have provided important
insight into how P. aeruginosa utilization of phosphatidylcholine-derived products
alters P. aeruginosa-host interactions.
This image shows a blood agar plate with two strains capable of producing PlcH
(zones of hemolysis) and one strain that does not.
 Through our work and work by other labs, a number of molecules that inhibit
Ras signaling in C. albicans have been identified (Davis-Hanna, 2008). We are
interested in the mechanism by which inhibition of the Ras1-cAMP pathway occurs
and how responses to these signaling molecules are fine tuned. We are also
very interested in understanding the ecological role for the modulation of
Ras signaling in single species and mixed species communities.
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