Kolter Lab

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Department of Microbiology and Molecular Genetics - Harvard Medical School
Claudio AguilarVanja Klepac-Ceraj

Microbial community composition and dynamics in cystic fibrosis lung infections

Genetic disease cystic fibrosis (CF) is caused by a mutation in both copies of a single gene that results in production of a defective chloride channel (CFTR).  In the CF lungs, lack of this chloride channel results in abnormally viscous mucus, providing an environment permissive for chronic bacterial infections.  The bacterial pathogens in CF airways have been primarily characterized through cultivation of expectorated mucus on selective media, and have identified pathogens such as Burkholderia cepacia, Stenotrophomonas maltophila,Haemophilus influenzae, Staphylococcus aureus and Pseudomonas aeruginosa.  Culture-based methods, however, usually fail to detect all of the bacterial species in any given environment.  Our goal is to thoroughly determine the microbial community composition in the CF lung and then observe how this community changes over time, such as with antibiotic treatment, using culture-independent molecular biology-based techniques, including gene cloning and sequencing and microarray technology.

Evolution and diversity of Pseudomonas aeruginosa in environment

Of all the bacteria present in the environment, P. aeruginosa appears to be the most adept colonizer of CF airways as evidenced by the fact that >90% of people with CF become infected with this bacterium.  Yet, the specific factors that make P. aeruginosa the most prevalent cause of CF pulmonary infections remain unknown.  Genomic analyses of P. aeruginosa isolates indicate that this organism has a highly conserved genome.  Although this very catabolically versatile organism is considered ubiquitous, it is relatively difficult to isolate from the environment.  Using a suite of culture-based methods and molecular biology tools and comparative genomics approach, we are addressing a number of questions regarding the ecology and evolution of this fascinating microorganism.  For example, (1) How old is the P. aeruginosa genome?  (2) What environmental forces define this highly conserved genome?  (3) What are survival strategies of P. aeruginosa in the environment?, and (4) What is the spatial and temporal diversity of naturally occurring P. aeruginosa populations?