Bioengineered lysozyme in combination therapies for<i>Pseudomonas aeruginosa</i>lung infections

Griswold, Karl E.; Bement, Jenna; Tenebäck, Charlotte C.; Scanlon, Thomas C.; Wargo, Matthew J.; Leclair, Laurie W

doi:10.4161/bioe.28335

Cited by 27 publications

(25 citation statements)

References 28 publications

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“…The effectiveness of lysozyme is also reduced in biofilms and in the chronically infected lung, due to electrostatic sequestration of the enzyme by infection-associated anionic biopolymers 24 , 25 . This was clear when LESB65 was grown in ASM, where it showed complete resistance to lysozyme at all concentrations tested (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa

et al. 2018

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Pseudomonas aeruginosa colonises the upper airway of cystic fibrosis (CF) patients, providing a reservoir of host-adapted genotypes that subsequently establish chronic lung infection. We previously experimentally-evolved P. aeruginosa in a murine model of respiratory tract infection and observed early-acquired mutations in pmrB, encoding the sensor kinase of a two-component system that promoted establishment and persistence of infection. Here, using proteomics, we show downregulation of proteins involved in LPS biosynthesis, antimicrobial resistance and phenazine production in pmrB mutants, and upregulation of proteins involved in adherence, lysozyme resistance and inhibition of the chloride ion channel CFTR, relative to wild-type strain LESB65. Accordingly, pmrB mutants are susceptible to antibiotic treatment but show enhanced adherence to airway epithelial cells, resistance to lysozyme treatment, and downregulate host CFTR expression. We propose that P. aeruginosa pmrB mutations in CF patients are subject to an evolutionary trade-off, leading to enhanced colonisation potential, CFTR inhibition, and resistance to host defences, but also to increased susceptibility to antibiotics.

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Section: Resultsmentioning

confidence: 99%

Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa

et al. 2018

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“…137,138 This mutant lysozyme also displayed superior antibiotic activity to wild type in a murine P. aeruginosa lung infection model. 139,140 There was substantial variation in P. aeruginosa killing by lysozyme both with and without the presence of polyanions throughout the screen, emphasizing that (as with the charged peptide assay in Fig. 5b 131 ) net charge is not sufficient to determine the strength of electrostatic binding; context and charge placement are important as well.…”

Section: Interactive Filtersmentioning

confidence: 99%

The particle in the spider's web: transport through biological hydrogels

2017

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Biological hydrogels such as mucus, extracellular matrix, biofilms, and the nuclear pore have diverse functions and compositions, but all act as selectively permeable barriers to the diffusion of particles. Each barrier has a crosslinked polymeric mesh that blocks penetration of large particles such as pathogens, nanotherapeutics, or macromolecules. These polymeric meshes also employ interactive filtering, in which affinity between solutes and the gel matrix controls permeability. Interactive filtering affects the transport of particles of all sizes including peptides, antibiotics, and nanoparticles and in many cases this filtering can be described in terms of the effects of charge and hydrophobicity. The concepts described in this review can guide strategies to exploit or overcome gel barriers, particularly for applications in diagnostics, pharmacology, biomaterials, and drug delivery.

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“…A wide range of applications for lysozyme has been developed, such as the preservation of food products, potential antimicrobial agent, clinical diagnosis of diseases, antineoplastic agents, etc. [4][5][6][7]. Additionally, the anti-inflammatory, antibacterial, and antineoplastic activities make lysozyme a promising candidate in the application of pharmacological functions, and thus it has become an interesting research area [8].…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

Wang

Jin

et al. 2020

IJMS

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The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. Lysozyme degrades bacterial cell wall without involving antibiotic resistance and has become a new antibacterial strategy. However, direct use of native, active proteins in clinical settings is not practical as it is fragile under various conditions. In this study, lysozyme was integrated into chitosan nanoparticles (CS-NPs) by the ionic gelation technique to obtain lysozyme immobilized chitosan nanoparticles (Lys-CS-NPs) and then characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), which showed a small particle size (243.1 ± 2.1 nm) and positive zeta potential (22.8 ± 0.2 mV). The immobilization significantly enhanced the thermal stability and reusability of lysozyme. In addition, compared with free lysozyme, Lys-CS-NPs exhibited superb antibacterial properties according to the results of killing kinetics in vitro and measurement of the minimum inhibitory concentration (MIC) of CS-NPs and Lys-CS-NPs against Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus). These results suggest that the integration of lysozyme into CS-NPs will create opportunities for the further potential applications of lysozyme as an anti-bacterium agent.

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Bioengineered lysozyme in combination therapies forPseudomonas aeruginosalung infections

Cited by 27 publications

References 28 publications

Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa

Evolutionary trade-offs associated with loss of PmrB function in host-adapted Pseudomonas aeruginosa

The particle in the spider's web: transport through biological hydrogels

Enhancing the Thermo-Stability and Anti-Bacterium Activity of Lysozyme by Immobilization on Chitosan Nanoparticles

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