Adaptation and Evolution of Pathogens in the Cystic Fibrosis Lung

Abstract

As opposed to acute respiratory infections, the persistent bacterial infections of the lung that characterize cystic fibrosis (CF) provide ample time for bacteria to evolve and adapt. The process of adaptation is recorded in mutations that accumulate over time in the genomes of the infecting bacteria. Some of these mutations lead to obvious phenotypic differences such as antibiotic resistance or the well-known mucoid phenotype of Pseudomonas aeruginosa. Other mutations may be just as important but harder to detect such as increased mutation rates, cell surface changes, and shifts in metabolism and nutrient acquisition. Remarkably, many of the adaptations occur again and again in different patients, signaling that bacteria are adapting to solve specific challenges in the CF respiratory tract. This parallel evolution even extends across distinct bacterial species. This review addresses the bacterial systems that are known to change in long-term CF infections with a special emphasis on cross-species comparisons. Consideration is given to how adaptation may impact health in CF, and the possible evolutionary mechanisms that lead to the repeated parallel adaptations.

Structure-preserving fixation allows Scanning Electron Microscopy to reveal biofilm microstructure and interactions with immune cells

“…As illustrative examples of biofilm types, we use biofilms grown from two lab strains of P. aeruginosa , PA01 wild type (denoted WT) and mutant PW2387 (genotype mucA-A05:ISphoA/hah) [26] (denoted Alginate+). Alginate+ overexpresses the anionic polysaccharide alginate, whose production in CF airways has been associated with infection persistence and poor clinical condition of patients [27, 28]. A standard glutaraldehyde-based fixative (“Standard Fix” in Table 1) is commonly used to preserve proteins [22].…”

Structure‐preserving fixation allows scanning electron microscopy to reveal biofilm microstructure and interactions with immune cells

“…As illustrative examples of biofilm types, we use biofilms grown from two lab strains of P. aeruginosa , PA01 wild‐type (denoted WT) and mutant PW2387 (genotype mucA‐A05:ISphoA/hah ) (denoted Alginate+). Alginate+ overexpresses the anionic polysaccharide alginate, whose production in CF airways has been associated with infection persistence and poor clinical condition of patients 39,40 . A standard glutaraldehyde‐based fixative (‘Standard Fix’ in Table 1) is commonly used to preserve proteins 34 .…”

“…Alginate+ overexpresses the anionic polysaccharide alginate, whose production in CF airways has been associated with infection persistence and poor clinical condition of patients. 39,40 A standard glutaraldehyde-based fixative ('Standard Fix' in Table 1) is commonly used to preserve proteins. 34 Glutaraldehyde molecules each possess two aldehyde groups separated by a chain of three methylene bridges.…”

Physiological Concentrations of Calcium Interact with Alginate and Extracellular DNA in the Matrices of Pseudomonas aeruginosa Biofilms to Impede Phagocytosis by Neutrophils

“…1−3 An established biofilm infection is difficult to eradicate and is frequently associated with poor patient prognosis in CF. 1,4,5 Persistence of chronic P. aeruginosa infections in CF patients is largely associated with the so-called "mucoid" biofilms that produce high amounts of the matrix polysaccharide alginate. 5 Other matrix components that can be produced by P. aeruginosa are the polysaccharides Pel and Psl and extracellular DNA (eDNA).…”

“…Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen known for producing robust biofilms, notably in chronic wounds and in the airways of persons with cystic fibrosis (CF). − An established biofilm infection is difficult to eradicate and is frequently associated with poor patient prognosis in CF. ,, Persistence of chronic P. aeruginosa infections in CF patients is largely associated with the so-called “mucoid” biofilms that produce high amounts of the matrix polysaccharide alginate .…”