Human lysozyme peptidase resistance is perturbed by the anionic glycolipid biosurfactant rhamnolipid produced by the opportunistic pathogen Pseudomonas aeruginosa
| Autor: | Jan J. Enghild, Kell K. Andersen, Brian S. Vad, Carsten Scavenius, Daniel E. Otzen |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Anions
Models Molecular 0301 basic medicine Virulence Factors Proteolysis Static Electricity Virulence Biology medicine.disease_cause Biochemistry Mass Spectrometry Bacterial cell structure Microbiology 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Protein Domains medicine Humans Secretion Pancreatic Elastase medicine.diagnostic_test Pseudomonas aeruginosa Circular Dichroism Elastase Rhamnolipid 030104 developmental biology chemistry Biofilms Electrophoresis Polyacrylamide Gel Muramidase Glycolipids Lysozyme Peptide Hydrolases Protein Binding |
| Zdroj: | Andersen, K K, Vad, B S, Scavenius, C, Enghild, J J & Otzen, D E 2017, ' Human lysozyme peptidase resistance is perturbed by the anionic glycolipid biosurfactant rhamnolipid produced by the opportunistic pathogen Pseudomonas aeruginosa ', Biochemistry, vol. 56, no. 1, pp. 260–270 . https://doi.org/10.1021/acs.biochem.6b01009 |
| Popis: | Infection by the opportunistic pathogen Pseudomonas aeruginosa (PA) is accompanied by the secretion of virulence factors such as the secondary metabolite rhamnolipid (RL) as well as an array of bacterial enzymes, including the protease elastase. The human immune system tries to counter this via defensive proteins such as human lysozyme (HLZ). HLZ targets the bacterial cell wall but may also have other antimicrobial activities. The enzyme contains four disulfide bonds and shows high thermodynamic stability and resistance to proteolytic attack. Here we show that RL promotes HLZ degradation by several unrelated proteases, including the PA elastase and human proteases. This occurs although RL does not by itself denature HLZ. Nevertheless, RL binds in a sufficiently high stoichiometry (8 RL:1 HLZ) to neutralize the highly cationic surface of HLZ. The initial cleavage sites agree well with the domain boundaries of HLZ. Thus, RL binding to native HLZ may be sufficient to allow proteolytic attack at slightly exposed sites on the protein, leading to subsequent degradation. Furthermore, biofilms of RL-producing strains of PA are protected better against high concentrations of HLZ than RL-free PA strains. We conclude that pathogen-produced RL may weaken host defenses by facilitating degradation of key host proteins. |
| Databáze: | OpenAIRE |
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