Same Game, Different Players: Emerging Pathogens of the CF Lung

Abstract

The survival rates of individuals with cystic fibrosis (CF) have significantly increased as a result of improved therapies, such as the inclusion of cystic fibrosis transmembrane conductance regulator (CFTR) modulators for some mutations. However, microbial infection of the airways remains a significant clinical problem. The well-known pathogens Pseudomonas aeruginosa and Staphylococcus aureus continue to establish difficult-to-treat infections in the CF lung. However, in recent years, there has been an increased prevalence of both Aspergillus fumigatus (Af) and non-tuberculous mycobacteria (NTM) species isolated from CF patient sputa. The emergence of these pathogens opens an important area of discussion about multikingdom infections, specifically, how interspecies interactions have the potential to shape the course of infection, such as tolerance to host immune defenses and antimicrobial therapies. Their ability to establish themselves in an existing polymicrobial environment suggests to us that microbial interactions play a significant role, and characterizing these mechanisms and understanding their implications will be critical to the future development of better antimicrobial therapies. With this minireview, we hope to inspire conversations about and demonstrate the merit of more research in this area. IMPORTANCE Incidences of non-tuberculous mycobacteria (NTM) and Aspergillus fumigatus have increased around the world over the past decade and have become a significant health threat to immunocompromised individuals such as those with cystic fibrosis (CF). CF is characterized by the buildup of mucus in the lungs which become chronically infected by a myriad of pathogens. The emergence of these pathogens in established infection sites raises many questions about the microbial ecosystems they become a part of, specifically how changes in these ecosystems impact disease outcomes. Understanding how microbial communities establish and maintain themselves despite medical treatment and host immune defenses will be critical for the development of improved therapeutic strategies.

Nontuberculous Mycobacteria: Ecology and Impact on Animal and Human Health

“…Pulmonary mycobacteriosis is severe in individuals with a predisposition to infection and in individuals with comorbidities in the United States [ 22 ], South Korea [ 23 , 24 ], and China [ 25 ]. In particular, patients with cystic fibrosis are predisposed to colonization and NTM infection [ 26 , 27 ].…”

Nontuberculous Mycobacterial Lung Disease in the Patients with Cystic Fibrosis—A Challenging Diagnostic Problem

“…Additionally, some CF patients colonized with A. fumigatus , are recognized with ABPA and treated with oral steroids. ABPA was listed as another possible risk factor for NTM isolation [ 10 , 13 , 30 ]. In the present study group, 46% of the patients were diagnosed with ABPA, prior to NTM isolation.…”

CFTR Modulator Therapies: Potential Impact on Airway Infections in Cystic Fibrosis

“…The use of aggressive antibiotic therapy and airway clearance, as well as the implementation of infection control guidelines had a key role in CF infection control; however, airway infection prevention and treatment continue to represent a relevant challenge in both children and adults with CF [ 21 ]. Whether and how the recent introduction in clinical practice of CFTR modulator therapy will affect the development and progression of airway infections in CF patients is still at the beginning of being deciphered.…”

“…The advent of next-generation sequencing (NGS) and the increased interest in the study of the microbial communities and microbiome had led to the knowledge that the co-existence of other microorganisms can influence P. aeruginosa infection characteristics and promote or hamper the infection chronicization [ 35 , 36 ]. Moreover, CF polymicrobial communities can influence antimicrobial resistance, expression of virulence factors and response to antimicrobial therapy, potentially leading to a poorer clinical outcome [ 18 , 21 , 35 , 36 , 37 ].…”