Human lysozyme peptidase resistance is perturbed by the anionic glycolipid biosurfactant rhamnolipid produced by the opportunistic pathogen Pseudomonas aeruginosa

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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.

Original languageEnglish
JournalBiochemistry
Volume56
Issue1
Pages (from-to)260–270
ISSN0006-2960
DOIs
Publication statusPublished - 2017

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