Cystic fibrosis is caused by mutations in the CFTR gene leading to a disrupted chloride channel. It is well established that the greatest contributor to patient morbidity and mortality is chronic lung disease, caused by a constant cycle of infection and inflammation throughout the patient’s life. The CFTR mutation leads to defective regulation of chloride and sodium, resulting in increased water absorption, depletion of airway surface liquid and dehydrated mucous. Consequently, the purulent sputum and mucus plugs together with an ineffective inflammatory response, all contribute to the chronic infections that are central to CF lung disease. From early childhood, CF patients experience recurrent pulmonary infections from a range of pathogens.
In spite of intensive antibiotic therapy, certain organisms persist, leading to pulmonary exacerbations, hospitalizations and patient death. These include Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and Achromobacter xylosoxidans, with Bcc being the most problematic. It was recently demonstrated that chronic colonisation by Bcc resulted in a greater lung function decline than by the other two pathogens. CF patients are also susceptible to colonisation by other pathogens, including Staphylococcus aureus (both methicillin-resistant and sensitive), genus Pandoraea, Stenotrophomonas maltophilia and non-tuberculous Mycobacteria, although the role of these latter four pathogens in CF lung disease is unclear. Furthermore, the identification of high levels of anaerobic organisms in CF sputum has added to the complex microbial population in the CF lung. These CF-associated anaerobes were not susceptible to antibiotics with known efficacy against anaerobes and the clinical significance of anaerobes in CF is not yet fully understood.
Bacterial host interactions in cystic fibrosis. Curr Opin Microbiol. Dec 1 2011
Chronic infection is a hallmark of cystic fibrosis (CF) and the main contributor to morbidity. Microbial infection in CF is complex, due to the number of different species that colonise the CF lung. Their colonisation is facilitated by a host response that is impaired or compromised by highly viscous mucous, zones of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR). Successful dominant CF pathogens combine an effective arsenal to establish infection and counter-attack the host response, together with an ability to adapt readily to an unfavourable environment. Hypermutability is common among CF pathogens facilitating adaptation and as the host response persists, progressive destruction of the normal architecture of lung tissue ensues with catastrophic consequences for the host.