Cystic Fibrosis Patients Infected With Epidemic Pseudomonas aeruginosa Strains Have Unique Microbial Communities

Abstract

Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, the clinical course experienced by infected individuals varies markedly. Understanding these differences is imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients infected with epidemic P. aeruginosa (ePA) strains may have a worse clinical prognosis than those infected with unique, non-clonal strains. Additionally, the traditionally uncultured CF lung bacterial community (i.e., CF microbiome) may further influence the outcome. We sought to identify if these two important variables, not identified through routine culture, associate and together may contribute to disease pathogenesis. Patients were classified as being infected with Prairie Epidemic ePA (PES) or a non-clonal strain, unique PA strains (uPA), through a retrospective assessment of a comprehensive strain biobank using a combination of PFGE and PES-specific PCR. Patients were matched to age, sex, time-period controls and sputum samples from equivalent time periods were identified from a sputum biobank. Bacterial 16S rRNA gene profiling and Pseudomonas qPCR was used to characterize the respiratory microbiome. We identified 31 patients infected with PES and matched them with uPA controls. Patients infected with PES at baseline have lower microbial diversity (P = 0.02) and higher P. aeruginosa relative abundance (P < 0.005). Microbial community structure was found to cluster by PA strain type, although it was not the main determinant of community structure as additional factors were also found to be drivers of CF community structure. Communities from PES infected individuals were enriched with Pseudomonas, Streptococcus and Prevotella OTUs. The disproportionate disease experienced by ePA infected CF patients may be mediated through a combination of pathogen-pathogen factors as opposed to strictly enhanced virulence of infecting P. aeruginosa strains.

Insights into the Adolescent Cystic Fibrosis Airway Microbiome Using Shotgun Metagenomics

“…In this study, we found the well-known CF bacteria P. aeruginosa, S. aureus, H. influenzae, H. parainfluenzae and S. maltophilia to be some of the most abundant species across most samples, mirroring decades of culture data. A number of Streptococcus spp were also among the most abundant species in our samples and have been detected in previous CF microbiome studies [6,29]. We identified two Gemella species, a Prevotella species, three Rothia species and three Veillonella species among the most abundant bacteria present in our samples, and none of these bacteria were detected by culture.…”

Resistance Is Not Futile: The Role of Quorum Sensing Plasticity in Pseudomonas aeruginosa Infections and Its Link to Intrinsic Mechanisms of Antibiotic Resistance

“…While the host microbiome does not appear to influence the pathogenicity of P. aeruginosa, the pathogen can affect the microbial diversity of a patient. Patients infected with an epidemic strain of P. aeruginosa had lower microbial diversity and enrichment of other lung pathogens, such as Streptococcus spp., indicating that enhanced pathogenesis of certain strains can be the result of not only the infecting strain of P. aeruginosa, but might also be related to pathogen-pathogen interactions in the lung [128].…”

Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis

“…According to studies, approximately 27% of patients with CF aged 2-5 years and 60 to 70% of adult patients are infected with P. aeruginosa, a Gramnegative bacterium found in many natural and artificial water sources [2]. Due to its opportunistic nature, this bacterium is regarded as the most critical CF pathogen [3]. The development of new antibiotics or innovative therapeutic approaches for treating P. aeruginosa infections is imperatively required for patients whose infections are resistant to currently available antibiotics.…”