Ecological Succession of Polymicrobial Communities in the Cystic Fibrosis Airways

Abstract

Antimicrobial therapies against cystic fibrosis (CF) lung infections are largely aimed at the traditional, well-studied CF pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex, despite the fact that the CF lung harbors a complex and dynamic polymicrobial community. A clinical focus on the dominant pathogens ignores potentially important community-level interactions in disease pathology, perhaps explaining why these treatments are often less effective than predicted based on in vitro testing. A better understanding of the ecological dynamics of this ecosystem may enable clinicians to harness these interactions and thereby improve treatment outcomes. Like all ecosystems, the CF lung microbial community develops through a series of stages, each of which may present with distinct microbial communities that generate unique host-microbe and microbe-microbe interactions, metabolic profiles, and clinical phenotypes. While insightful models have been developed to explain some of these stages and interactions, there is no unifying model to describe how these infections develop and persist. Here, we review current perspectives on the ecology of the CF airway and present the CF Ecological Succession (CFES) model that aims to capture the spatial and temporal complexity of CF lung infection, address current challenges in disease management, and inform the development of ecologically driven therapeutic strategies.

Keywords: Pseudomonas aeruginosa; anaerobic bacteria; cystic fibrosis; ecological succession; microbial ecology; microbiome; polymicrobial infections; pulmonary exacerbations.

FIG 1

Model of ecological succession describing the stages of primary succession (left) that occurs through pioneer species which colonize an initially uninhabited landscape from an environmental reservoir secondary succession (right) that occurs through locally resident species following a perturbation that disrupts the normal steady state and results in the formal of a stable, but different climax community. As the perturbations, however minor, are constantly occurring, even a relatively “steady-state” community is constantly in a dynamic state of flux, and moving toward a desired equilibrium, which may never be truly reached. The image was created with BioRender.

FIG 2

CFES model showing progressive changes to the lungs over time and disease development. Each stage of development corresponds to an analogous stage of succession shown in Fig. 1, along with the microbial taxa frequently observed in the lung at that stage. The two gradients below the lung diagrams illustrate traits that progressively change during the stages of succession, with light gray and dark gray indicating low and high levels, respectively. (Copyright Maggie Middleton.)