Introduction to Cystic Fibrosis Microbiology

Cystic fibrosis (CF) is the most common autosomal recessive disorder in the United Kingdom, with a carrier rate of 1 in 25 and an incidence of 1 in 2,500 live births. With a present life expectancy of approximately 31 years (higher if lung infections are avoided) and a median age of death of 24, children and young adults comprise most of the 7,500 people within the UK who have this chronic and progressive multi-system condition.

CF is caused by mutations within the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that is essential for the regulation of salt and water movements across epithelial membranes. Whilst CF is a multi-system condition, the most important cause of morbidity and mortality are recurrent respiratory infections, inflammatory lung disease and ultimately respiratory failure. These arise mainly as a consequence of viscous airway secretions which impair mucociliary clearance of bacterial pathogens. Invasive infection of other sites in the CF patient is uncommon.

The microbiology of CF is challenging and complex. Surprisingly few bacterial pathogens succeed in establishing infection within the CF lung. Major CF pathogens include Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, and more recently, Burkholderia cepacia complex (Bcc) which was originally identified as a plant pathogen and the causative agent of soft onion rot (Fig. 1).

Fig. 1: Soft onion rot caused by Burkholderia cepacia complex (Bcc) organisms. The two onions at the top of the figure have been inoculated with environmental (left) and clinical (right) isolates of B. cenocepacia. Below is an uninfected control.

Other potential emerging pathogens, which are isolated with increasing frequency, include atypical mycobacteria, Stenotrophomonas maltophilia and Achromobacter xylosoxidans. P. aeruginosa is the most common and important cause of chronic infection within the CF lung, and with Bcc organisms are the most problematic in terms of eradication and treatment. If early P. aeruginosa infection is left untreated or eradication is unsuccessful the early infecting isolates of P. aeruginosa which are typically non-mucoid and relatively sensitive to antimicrobial therapy are superseded by mucoid strains that overproduce the exopolysaccharide alginate (Fig. 2 & 3).

Fig. 2: (A) Non-mucoid (left) and mucoid (right) strains of P. aeruginosa isolated from the CF lung. (B) Bacterial growth obtained from sputum, showing the initial emergence of mucoid P. aeruginosa.	Fig. 3: The exopolysaccharide alginate produced by P. aeruginosa.

This mucoid phenotype, coupled with the growth of P. aeruginosa in biofilms (Fig. 4), hinders the effectiveness of antimicrobial therapy and phagocytic clearance.

Fig. 4: Biofilm growth of P. aeruginosa within the CF lung presents a challenge to phagocytic cells.

Bcc exhibit striking and inherent multiresistance to most antimicrobial agents, are highly inflammatory and are capable of surviving intracellularly within activated phagocytic cells. In addition, some Bcc species, in particular Burkholderia cenocepacia and Burkholderia multivorans have proved to be highly transmissible between CF patients. Thus, although these organisms have only recently emerged as human pathogens and are considerably less prevalent than P. aeruginosa within the CF population, they are an important cause of anxiety for CF individuals and their carers.

In individual CF patients, prevention of chronic infection prevents or slows deterioration of lung function, thus improving survival and quality of life. Effective treatment is therefore directed at the early identification and eradication of bacterial infections from the CF airways to prevent the onset of chronic infection. Indeed, improved antibiotic treatment strategies are the principal reason for the increased life expectancy observed within CF patients in recent decades. Unfortunately, increasing resistance to antibiotics in general, and the emergence of highly adaptable lineages of transmissible 'CF superbugs', has compromised the efficacy of many antibiotics, at least in terms of bacterial killing, and required urgent attention to other forms of cross-infection control. Whilst successful antibiotic therapy in CF remains an important aim, the eradication of Bcc and multiresistant P. aeruginosa is challenging. Thus, the current strategy to prevent cross infection between CF patients includes a draconian policy of segregating infected and non-infected individuals. The exclusion and social stigma caused by such measures restricts social interaction, especially between CF siblings, and may lead to anxiety and further deterioration in quality of life.

Further information:

The Publication Library of the CF Trust contains many relevant consensus documents including:

Burkholderia cepacia Complex. Suggestions for Prevention and Infection Control. Report of the UK Cystic Fibrosis Infection Control Group. Second Edition. September 2004

Pseudomonas aeruginosa infection in people with Cystic Fibrosis. Suggestions for Prevention and Infection Control. Report of the Cystic Fibrosis Trust Infection Control Group. Second Edition. November 2004.

Antibiotic treatment for Cystic Fibrosis. Second edition. Report of the UK Cystic Fibrosis Trust Antibiotic Group. September 2002.