Lysozyme Activity in Cystic Fibrosis

Hughes, Walter T.; Koblin, Beryl A.; Rosenstein, Beryl J.

doi:10.1203/00006450-198210000-00014

Cited by 11 publications

(5 citation statements)

References 16 publications

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“…In vivo concentrations of specific AMPs have been reported to vary due to an individual's age and/or their underlying conditions. For example, CF patients have been reported to have higher levels of lysozyme and lactoferrin in bronchoalveolar lavage fluid in comparison to healthy controls [53][54][55]. The bronchoalveolar lavage fluid of new born infants during pulmonary or systemic infection has been described to have significantly increased levels of β-defensin-1, β-defensin-2 and LL-37 in comparison to healthy controls [56].…”

Section: Discussionmentioning

confidence: 99%

Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus

Ballard

Yucel

Melchers

et al. 2020

JoF

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Antimicrobial peptides and proteins (AMPs) provide an important line of defence against invading microorganisms. However, the activity of AMPs against the human fungal pathogen Aspergillus fumigatus remains poorly understood. Therefore, the aim of this study was to characterise the anti-Aspergillus activity of specific human AMPs, and to determine whether A. fumigatus can possess resistance to specific AMPs, as a result of in-host adaptation. AMPs were tested against a wide range of clinical isolates of various origins (including cystic fibrosis patients, as well as patients with chronic and acute aspergillosis). We also tested a series of isogenic A. fumigatus isolates obtained from a single patient over a period of 2 years. A range of environmental isolates, obtained from soil in Scotland, was also included. Firstly, the activity of specific peptides was assessed against hyphae using a measure of fungal metabolic activity. Secondly, the activity of specific peptides was assessed against germinating conidia, using imaging flow cytometry as a measure of hyphal growth. We showed that lysozyme and histones inhibited hyphal metabolic activity in all the A. fumigatus isolates tested in a dose-dependent fashion. In addition, imaging flow cytometry revealed that histones, β-defensin-1 and lactoferrin inhibited the germination of A. fumigatus conidia.

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Section: Discussionmentioning

confidence: 99%

Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus

Ballard

Yucel

Melchers

et al. 2020

JoF

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“…However, we have recently shown (17) that there is no significant difference in immunological concentrations of HAL in cystic fibrosis sputa regardless of their P. aeruginosa numeration. This may be due to either a HAL release secondary to an increased granulocyte turnover observed in chronic bacterial infection of the respiratory tract (16) or to an inactivation of P. aeruginosa E. Recently, Doring et al (6) have suggested that specific antibodies to P. aeruginosa E might neutralize the proteolytic activity of this elastase in vivo. According to these authors, P. aeruginosa E was only detected in bronchial secretions from cystic fibrosis patients when antibodies to this elastase were lacking in sera and bronchial secretions.…”

Section: 4kmentioning

confidence: 99%

In vitro evidence that human airway lysozyme is cleaved and inactivated by Pseudomonas aeruginosa elastase and not by human leukocyte elastase

Jacquot¹,

Tournier²,

Puchelle³

1985

Infect Immun

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The in vitro effects of Pseudomonas aeruginosa elastase (P. aeruginosa E) and of human leukocyte elastase on human airway lysozyme (HAL) were investigated. P. aeruginosa E inactivated and cleaved HAL, whereas human leukocyte elastase had no effect. Total inactivation of HAL by P. aeruginosa E was observed after 120 min of incubation at 37°C, for an elastase-to-lysozyme molar ratio of 1:5. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing HAL and P. aeruginosa E in an elastase-to-lysozyme molar ratio of 1:10 showed a progressive disappearance of the HAL band upon increasing the incubation time with P. aeruginosa E. Gel filtration chromatography indicated that HAL was cleaved into at least three peptide fragments. The cleavage of HAL by P. aeruginosa E was accompanied by parallel losses of its bacteriolytic activity and its immunoreactive property. 555 on July 15, 2020 by guest http://iai.asm.org/ Downloaded from

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“…Although lysozyme has been proposed to play a crucial role in host defense, persistent P. aeruginosa airway infection is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. Moreover, higher lysozyme activity has been detected in the serum and saliva of CF patients compared with normal individuals (Hughes et al, 1982 ). Likewise, lysozyme activity was also higher in bronchoalveolar lavage fluid (BALF) collected from CF patients (Sagel et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosa Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics

Lee

et al. 2017

Front. Cell. Infect. Microbiol.

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Pseudomonas aeruginosa is capable of establishing airway infections. Human airway mucus contains a large amount of lysozyme, which hydrolyzes bacterial cell walls. P. aeruginosa, however, is known to be resistant to lysozyme. Here, we performed a genetic screen using a mutant library of PAO1, a prototype P. aeruginosa strain, and identified two mutants (ΔbamB and ΔfabY) that exhibited decrease in survival after lysozyme treatment. The bamB and fabY genes encode an outer membrane assembly protein and a fatty acid synthesis enzyme, respectively. These two mutants displayed retarded growth in the airway mucus secretion (AMS). In addition, these mutants exhibited reduced virulence and compromised survival fitness in two different in vivo infection models. The mutants also showed susceptibility to several antibiotics. Especially, ΔbamB mutant was very sensitive to vancomycin, ampicillin, and ceftazidime that target cell wall synthesis. The ΔfabY displayed compromised membrane integrity. In conclusion, this study uncovered a common aspect of two different P. aeruginosa mutants with pleiotropic phenotypes, and suggests that BamB and FabY could be novel potential drug targets for the treatment of P. aeruginosa infection.

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Lysozyme Activity in Cystic Fibrosis

Cited by 11 publications

References 16 publications

Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus

Antifungal Activity of Antimicrobial Peptides and Proteins against Aspergillus fumigatus

In vitro evidence that human airway lysozyme is cleaved and inactivated by Pseudomonas aeruginosa elastase and not by human leukocyte elastase

A Genetic Screen Reveals Novel Targets to Render Pseudomonas aeruginosa Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics

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