Serum proteases prevent bacterial biofilm formation: role of kallikrein and plasmin
Arenas, Jesús; Szabo, Zalan; van der Wal, Jelle; Maas, Coen; Riaz, Tahira; Tønjum, Tone; Tommassen, Jan
(2021) Virulence, volume 12, issue 1, pp. 2902 - 2917
(Article)
Abstract
Biofilm formation is a general strategy for bacterial pathogens to withstand host defense mechanisms. In this study, we found that serum proteases inhibit biofilm formation by Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, and Bordetella pertussis. Confocal laser-scanning microscopy analysis revealed that these proteins reduce the biomass and alter the architecture
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of meningococcal biofilms. To understand the underlying mechanism, the serum was fractionated through size-exclusion chromatography and anion-exchange chromatography, and the composition of the fractions that retained anti-biofilm activity against N. meningitidis was analyzed by intensity-based absolute quantification mass spectrometry. Among the identified serum proteins, plasma kallikrein (PKLK), FXIIa, and plasmin were found to cleave neisserial heparin-binding antigen and the α-peptide of IgA protease on the meningococcal cell surface, resulting in the release of positively charged polypeptides implicated in biofilm formation by binding extracellular DNA. Further experiments also revealed that plasmin and PKLK inhibited biofilm formation of B. pertussis by cleaving filamentous hemagglutinin. We conclude that the proteolytic activity of serum proteases toward bacterial adhesins involved in biofilm formation could constitute a defense mechanism for the clearance of pathogens.
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Keywords: biofilms, Bordetella pertussis, eDNA, FHA, IgA protease, kallikrein, NaLP, Neisseria meningitidis, NHBA, plasmin, serum proteases, Parasitology, Microbiology, Immunology, Microbiology (medical), Infectious Diseases
ISSN: 2150-5594
Publisher: Landes Bioscience
Note: Funding Information: The author(s) reported there is no funding associated with the work featured in this article. We would like to acknowledge Sander Ruiter and Jes?s P?rez-Ortega (Utrecht University) and Zoone Hofman (University Medical Center, Utrecht) for technical support, and Dr. Marien de Jonge (Institute for Molecular Life Sciences, Radboud UMC, Nijmegen) for kindly providing H. influenzae and S. aureus strains. We would also like to thank Prof. Suzan Rooijakkers (University Medical Center, Utrecht) and Prof. Ingrid de Meester (University of Antwerp) for providing several serum proteases used in preliminary screenings, and Drs. Mariagrazia Pizza (GSK, Sienna, Italy) and Fran?oise Jacob-Dubuisson (INSERM, Lille, France) for kindly providing antisera against NHBA and FHA, respectively. Publisher Copyright: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
(Peer reviewed)