Serum proteases prevent bacterial biofilm formation: role of kallikrein and plasmin

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 mic...

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Bibliographic Details
Published in:Virulence 2021-12, Vol.12 (1), p.2902-2917
Main Authors: Arenas, Jesús, Szabo, Zalan, van der Wal, Jelle, Maas, Coen, Riaz, Tahira, Tønjum, Tone, Tommassen, Jan
Format: Article
Language:eng ; nor
Subjects:
Adhesins, Bacterial - genetics
Biofilms
Bordetella pertussis
eDNA
FHA
Fibrinolysin - metabolism
IgA protease
kallikrein
Kallikreins - metabolism
NaLP
Neisseria meningitidis
Neisseria meningitidis - genetics
NHBA
plasmin
Research Paper
serum proteases
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Summary: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 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.
ISSN:2150-5594
2150-5608
DOI:10.1080/21505594.2021.2003115