Theories in Business and Information Systems Engineering

Even though the idea of science enjoys an impressive reputation, there seems to be no precise conception of science. On the one hand, there is no unified definition of the extension of activities subsumed under the notion of science. According to the narrow conception that is common in Anglo-Saxon countries, science is restricted to those disciplines that investigate nature and aim at explanation and prediction of natural phenomena. A wider conception that can be found in various European countries includes social sciences, the humanities and engineering. On the other hand and related to the first aspect, there is still no general consensus on the specific characteristics of scientific discoveries and scientific knowledge

Altering the viscoelastic properties of mucus-grown Pseudomonas aeruginosa biofilms affects antibiotic susceptibility

The viscoelastic properties of biofilms are correlated with their susceptibility to mechanical and chemical stress, and the airway environment in muco-obstructive pulmonary diseases (MOPD) facilitates robust biofilm formation. Hyperconcentrated, viscoelastic mucus promotes chronic inflammation and infection, resulting in increased mucin and DNA concentrations. The viscoelastic properties of biofilms are regulated by biopolymers, including polysaccharides and DNA, and influence responses to antibiotics and phagocytosis. We hypothesize that targeted modulation of biofilm rheology will compromise structural integrity and increase antibiotic susceptibility and mucociliary transport. We evaluate biofilm rheology on the macro, micro, and nano scale as a function of treatment with a reducing agent, a biopolymer, and/or tobramycin to define the relationship between the viscoelastic properties of biofilms and susceptibility. Disruption of the biofilm architecture is associated with altered macroscopic and microscopic moduli, rapid vector permeability, increased antibiotic susceptibility, and improved mucociliary transport, suggesting that biofilm modulating therapeutics will improve the treatment of chronic respiratory infections in MOPD

Characterization of cilia beat frequency and mucociliary transport in racetrack cultures.

A) Average cilia beat frequency for each quadrant of two separate cultures. B) Overall average cilia beat frequency from five cultures. C) Mean MCT rates of beads in PBS for five separately prepared and evaluated cultures. Data is representative of the average and standard deviation of ≥3 individual measurements.</p

This file contains supporting table and supporting figures.

This file contains supporting table and supporting figures.</p

Representation of MCTD imaging for transport of biofilms.

MCT occurs counterclockwise with n≥3 videos per quadrant per biofilm. Figure created with biorender.com.</p

Matrix of biofilm treatment combinations.

People with muco-obstructive pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often have acute or chronic respiratory infections that are difficult to treat due in part to the accumulation of hyperconcentrated mucus within the airway. Mucus accumulation and obstruction promote chronic inflammation and infection and reduce therapeutic efficacy. Bacterial aggregates in the form of biofilms exhibit increased resistance to mechanical stressors from the immune response (e.g., phagocytosis) and chemical treatments including antibiotics. Herein, combination treatments designed to disrupt the mechanical properties of biofilms and potentiate antibiotic efficacy are investigated against mucus-grown Pseudomonas aeruginosa biofilms and optimized to 1) alter biofilm viscoelastic properties, 2) increase mucociliary transport rates, and 3) reduce bacterial viability. A disulfide bond reducing agent (tris(2-carboxyethyl)phosphine, TCEP), a surfactant (NP40), a biopolymer (hyaluronic acid, HA), a DNA degradation enzyme (DNase), and an antibiotic (tobramycin) are tested in various combinations to maximize biofilm disruption. The viscoelastic properties of biofilms are quantified with particle tracking microrheology and transport rates are quantified in a mucociliary transport device comprised of fully differentiated primary human bronchial epithelial cells. The combination of the NP40 with hyaluronic acid and tobramycin was the most effective at increasing mucociliary transport rates, decreasing the viscoelastic properties of mucus, and reducing bacterial viability. Multimechanistic targeting of biofilm infections may ultimately result in improved clinical outcomes, and the results of this study may be translated into future in vivo infection models.</div

The non-Gaussian parameter κ as a function of treatment conditions for n≥4 separately prepared and evaluated biofilms.

Larger values are associated with increasing heterogeneity.</p

Triple combination treatment of PAO1 biofilms.

A) Biofilm complex viscosity distribution as a function of treatment conditions. Data is representative of every tracked particle complex viscosity for three separately prepared and evaluated specimens. B) Biofilm microscopic moduli as a function of treatment. The elastic modulus (G’, solid) and the viscous modulus (G”, dashed) are shown in green for the solid-like biofilm component and in blue for the more watery component as determined via Gaussian mixture modeling. C) Viability of PAO1 biofilms as a function of triple combination treatment. Significance was determined using single factor ANOVA with post hoc Tukey analysis. D) Mean MCT rates of biofilms as a function of triple combination treatment. Data is presented as the mean ± standard deviation of tracked particles for n≥6 videos. Significance was determined using single factor ANOVA with post hoc Tukey Kramer analysis.</p