Cystic Fibrosis Lung Infections: Polymicrobial, Complex, and Hard to Treat

Historically, H. influenzae and S. aureus were considered to be the primary organisms infecting the airways of infants and children with CF, followed by P. aeruginosa or Burkholderia cepacia complex during adulthood. These bacteria continue to play important roles in CF respiratory infections and clinical outcome; however, with the advent of improved culture methods and culture-independent approaches, including deep sequencing technology, it is clear that the airways of patients with CF are chronically colonized with complex, polymicrobial infections. In 2003, Rogers and colleagues revolutionized our understanding of CF lung infections through their identification of complex bacterial communities in sputum and bronchoscopy samples using a culture-independent, molecular-based approach, terminal restriction fragment length polymorphism profiling. This study was the first to recognize the role of highly prevalent and diverse bacterial species previously unrecognized in CF lung infections, including obligate anaerobes [1]. Since then, several additional studies utilizing culture-independent approaches have confirmed that the airways of patients with CF are chronically colonized with diverse bacterial, fungal, and viral taxa [2–5]. These polymicrobial communities are highly individualized to each patient and promote intricate inter-microbial and host—pathogen interactions, which alter the lung environment, impact response to treatment, and direct the course of disease (summarized in Fig 1). Core genera, including Streptococcus, Pseudomonas, Prevotella, Veillonella, Neisseria, Porphorymonas, and Catonella are detected in abundance in the majority of adult sputum samples [7]. In addition to this core, deep sequencing typically identifies 50–200 unique operational taxonomic units in a single CF respiratory sample. Furthermore, the advancement of molecular identification approaches has greatly enhanced our recognition of the diverse fungi (including Candida spp.,Malassezia spp., and Aspergillus spp.) and viruses (including influenza and respiratory syncytial virus) that co-inhabit the lungs of patients with CF [2,4,8]. Accompanying the explosion of organisms recognized in these multi-domain communities comes the task of determining the role of such microbes in CF lung disease. In the recently accepted context of highly individualized, complex, polymicrobial communities, answering the question of “who’s the pathogen?” has become a non-trivial challenge of both clinical diagnostic and academic research focus. Emerging pathogens (microbes that directly contribute to disease progression and poor patient outcome) of interest are bacterial (Streptococcusmilleri group spp., nontuberculous mycobacterium), fungal (Trichosporon spp.), and viral (rhinovirus). Meanwhile, other organisms previously considered to be pathogenic in the context of CF lung infections are now more widely thought of as normal microbiota and unlikely pathogens,