Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs-A Review

Abstract

Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages.

Figure 1

Time course of P. aeruginosa infection development. (a) Sputum colonization stage - P. aeruginosa equipped with full virulence factors enter in CF sputum; (b) Early infection stage—P. aeruginosa, which exhibit the environmental or wild-phenotypes species characteristics, starts its adaptation to CF environmental conditions; (c) Chronic infection stage—P. aeruginosa is full adapted to CF environment. At this stage, there is high phenotypic and genotypic diversity and formation of biofilms.

Figure 2

Representation of P. aeruginosa microevolution during infection in CF airways. At early stage of infection, P. aeruginosa is full equipped with cell-associated virulence factors, including flagella, pili, type 3 secretion systems (T3SS) and secreted virulence factors (e.g., proteases, pyoverdine, and rhamnolipid) and exhibit antibiotic sensitivity. At the chronic stage of infection, P. aeruginosa is fully adapted to CF environment and exhibits a variety of adaptations, including overproduction of alginate, loss of the implicated virulence factors for initial infection establishment, are resistant to antibiotics (expression of efflux pumps), and adapted metabolism. This microevolution occurs by the repeated interplay of mutation and selection.