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Infections with Pseudomonas aeruginosa in patients with cystic fibrosis
B Tümmler1, J Bosshammer, S Breitenstein
1Klinische Forschergruppe Molekulare Pathologie der Mukoviszidose, Zentrum Biochemie, Hannover, Germany.
Abstract:
The lung infection with Pseudomonas aeruginosa is regarded as one of the major causes of health decline in patients with cystic fibrosis (CF). The CF host response to the persistent bacterial antigen load in the endobronchiolar lumen is characterized by a pronounced humoral response, local production of cytokines, influx of neutrophils into the lung and a protease-protease inhibitor imbalance predominantly sustained by released neutrophil elastase. CF is an autosomal recessive disease, and we could demonstrate for our local patient population that the age-dependent risk to become chronically colonized with P. aeruginosa can be differentiated by the disease-causing CFTR mutation genotype. The age-specific colonisation rates were significantly lower in pancreas sufficient than in pancreas insufficient patients. P. aeruginosa is occasionally detected in throat swabs already in infancy or early childhood in most patients although there is a lapse of several years amenable to preventive measures such as vaccination until onset of persistent colonization. The epidemiology of the infection with P. aeruginosa was investigated by quantitative macrorestriction fragment pattern analysis. The distribution and frequency of clones found in CF patients match that found in other clinical and environmental aquatic habitats, but the over-representation of specific clones at a CF clinic indicates a significant impact of nosocomial transmission for the prevalence of P. aeruginosa-positive patients at a particular center. Most patients remain colonized with the initially acquired P. aeruginosa clone. According to direct sputum analysis the majority of patients is carrying a single clonal variant at a concentration of 10(7)-10(9) CFU. Co-colonization with other species or other clones is infrequent. Independent of the underlying genotype, the CF lung habitat triggers a uniform, genetically fixed conversion of bacterial phenotype. Most CFP, aeruginosa strains become non-motile, mucoid, LPS-, pyocin- and phage-deficient, secrete less virulence determinants and shift the production of cytokines evoked in neutrophils. On the other hand, other properties such as antimicrobial susceptibility or adherence to bronchial mucins remain highly variable reflecting the capacity of P. aeruginosa to adapt to ongoing changes in the CF lung habitat.
Insights
Pseudomonas aeruginosa lung infections significantly impact cystic fibrosis (CF) patients. Bacterial adaptation in the CF lung environment is uniform, despite variable host genotypes and strain characteristics.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Genetics
Background:
- Pseudomonas aeruginosa lung infection is a primary driver of health decline in cystic fibrosis (CF) patients.
- The CF host response involves inflammation, immune cell influx, and protease imbalance, largely driven by neutrophil elastase.
- CFTR mutation genotype influences the risk and age of chronic P. aeruginosa colonization.
Purpose of the Study:
- To investigate the relationship between CFTR mutation genotype and P. aeruginosa colonization risk.
- To analyze the epidemiology and transmission dynamics of P. aeruginosa in CF patients.
- To characterize the phenotypic adaptation of P. aeruginosa within the CF lung environment.
Main Methods:
- Quantitative macrorestriction fragment pattern analysis was used to study P. aeruginosa epidemiology.
- CFTR mutation genotype data was correlated with age-specific colonization rates.
- Bacterial phenotype analysis was performed on sputum samples from CF patients.
Main Results:
- Age-specific P. aeruginosa colonization rates were lower in pancreas-sufficient than pancreas-insufficient CF patients.
- Nosocomial transmission significantly impacts P. aeruginosa prevalence in CF clinics, with specific clones over-represented.
- CF P. aeruginosa strains uniformly adapt to the lung environment, becoming non-motile, mucoid, and altering virulence factor production, while maintaining variable antimicrobial susceptibility.
Conclusions:
- CFTR genotype and disease severity influence P. aeruginosa colonization risk.
- Understanding P. aeruginosa epidemiology and transmission is crucial for infection control in CF centers.
- P. aeruginosa exhibits remarkable adaptive capacity within the CF lung, leading to a conserved phenotypic conversion crucial for chronic infection.