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Abstract

Current therapy for cystic fibrosis (CF) focuses on minimizing
the microbial community and the host’s immune response through
the aggressive use of airway clearance techniques, broad-spectrum
antibiotics, and treatments that break down the pervasive endobronchial
biofilm.Antibiotic selection is typically based on the susceptibility
of individual microbial strains to specific antibiotics in vitro.
Often this approach cannot accurately predict medical outcomes
because of factors both technical and biological. Recent cultureindependent
assessments of the airway microbial and viral communities
demonstrated that the CF airway infection is considerably
more complex and dynamic than previously appreciated. Understanding
the ecological and evolutionary pressures that shape these
communities is critically important for the optimal use of current
therapies (in both the choice of therapy and timing of administration)
and the development of newer strategies. The climax–attack
model (CAM) presented here, grounded in basic ecological principles,
postulates the existence of two major functional communities.
The attack community consists of transient viral and microbial populations
that induce strong innate immune responses. The resultant
intense immune response creates microenvironments that facilitate
the establishment of a climax community that is slower-growing
and inherently resistant to antibiotic therapy. Newermethodologies,
including sequence-based metagenomic analysis, can track not only
the taxonomic composition but also the metabolic capabilities of
these changing viral andmicrobial communities over time. Collecting
this informationforCFairwayswill enable themathematicalmodeling
of microbial community dynamics during disease progression. The
resultant understanding of airway communities and their effects on
lung physiology will facilitate the optimization of CF therapies.