Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation
KAUST Grant NumberKUK-C1-017-12
Online Publication Date2012-12-04
Print Publication Date2013-01
Permanent link to this recordhttp://hdl.handle.net/10754/598670
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AbstractNeisseria meningitidis is a common and usually harmless inhabitant of the mucosa of the human nasopharynx, which, in rare cases, can cross the epithelial barrier and cause meningitis and sepsis. Biofilm formation favours the colonization of the host and the subsequent carrier state. Two different strategies of biofilm formation, either dependent or independent on extracellular DNA (eDNA), have been described for meningococcal strains. Here, we demonstrate that the autotransporter protease NalP, the expression of which is phase variable, affects eDNA-dependent biofilm formation in N.meningitidis. The effect of NalP was found in biofilm formation under static and flow conditions and was dependent on its protease activity. Cleavage of the heparin-binding antigen NhbA and the α-peptide of IgA protease, resulting in the release of positively charged polypeptides from the cell surface, was responsible for the reduction in biofilm formation when NalP is expressed. Both NhbA and the α-peptide of IgA protease were shown to bind DNA. We conclude that NhbA and the α-peptide of IgA protease are implicated in biofilm formation by binding eDNA and that NalP is an important regulator of this process through the proteolysis of these surface-exposed proteins. © 2012 Blackwell Publishing Ltd.
CitationArenas J, Nijland R, Rodriguez FJ, Bosma TNP, Tommassen J (2012) Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation. Molecular Microbiology 87: 254–268. Available: http://dx.doi.org/10.1111/mmi.12097.
SponsorsWe would like to thank Martine Bos and Vincent van Dam (Utrecht University), Peter van der Ley (Netherlands Vaccine Institute), Arie van der Ende (Amsterdam Medical Center) and GlaxoSmithKline Biologicals for strains, plasmids and antibodies used in this study. We gratefully acknowledge Tom Zalm, Florian Putker, Jan Grijpstra and Leticia Villalba (Utrecht University) for assistance in some of the experiments and Peter van Ulsen (Vrije Universiteit Amsterdam) for discussion. This work was supported by the Netherlands Organization for Health Research and Development (ZonMw). T.N.P.B. was partially supported by the King Abdullah University of Science and Technology (Grant No. № KUK-C1-017-12).