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Organisationseinheit der BAM
Pseudomonas aeruginosa biofilms exhibit an intrinsic resistance to antibiotics and constitute a considerable clinical threat. In cystic fibrosis, a common feature of biofilms formed by P. aeruginosa in the airway is the occurrence of mutants deficient in flagellar motility. This study investigates the impact of flagellum deletion on the structure and antibiotic tolerance of P. aeruginosa biofilms, and highlights a role for the flagellum in adaptation and cell survival during biofilm development. Mutations in the flagellar hook protein FlgE influence greatly P. aeruginosa biofilm structuring and antibiotic tolerance. Phenotypic analysis of the flgE knockout mutant compared to the wild type (WT) reveal increased fitness under planktonic conditions, reduced initial adhesion but enhanced formation of microcolony aggregates in a microfluidic environment, and decreased expression of genes involved in exopolysaccharide formation. Biofilm cells of the flgE knock-out mutant display enhanced tolerance towards multiple antibiotics, whereas its planktonic cells show similar resistance to the WT. Confocal microscopy of biofilms demonstrates that gentamicin does not affect the viability of cells located in the inner part of the flgE knock-out mutant biofilms due to reduced penetration. These findings suggest that deficiency in flagellar proteins like FlgE in biofilms and in cystic fibrosis infections represent phenotypic and evolutionary adaptations that alter the structure of P. aeruginosa biofilms conferring increased antibiotic tolerance.
Reliability analysis of deteriorating structural systems requires the solution of time-variant reliability problems.
In the general case, both the capacity of and the loads on the structure vary with time. This analysis can be approached by approximation through a series of time-invariant reliability problems, which is a potentially effective strategy for cases where direct solutions of the time-variant reliability problem are challenging, e.g. for structural systems with many elements or arbitrary load processes. In this contribution, we thoroughly Review the formulation of the equivalent time-invariant reliability problems and extend this approximation to structures for which inspection and monitoring data is available. Thereafter, we present methods for efficiently evaluating the reliability over time. In particular, we propose the combination of sampling-based methods with a FORM (first-order reliability method) approximation of the series system reliability problem that arises in the computation of the lifetime reliability. The framework and algorithms are demonstrated on a set of numerical examples, which include the computation of the reliability conditional on inspection data.