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Infection and Immunity, October 2008, p. 4649-4658, Vol. 76, No. 10
0019-9567/08/$08.00+0 doi:10.1128/IAI.00393-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
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Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands,1 Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands,2 Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, 1100 DD Amsterdam, The Netherlands,3 The Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM), 1100 DD Amsterdam, The Netherlands4
Received 28 March 2008/ Returned for modification 20 May 2008/ Accepted 29 July 2008
The two-partner secretion (TPS) pathway is widespread among gram-negative bacteria and facilitates the secretion of very large and often virulence-related proteins. TPS systems consist of a secreted TpsA protein and a TpsB protein involved in TpsA transport across the outer membrane. Sequenced Neisseria meningitidis genomes contain up to five TpsA- and two TpsB-encoding genes. Here, we investigated the distribution of TPS-related open reading frames in a collection of disease isolates. Three distinct TPS systems were identified among meningococci. System 1 was ubiquitous, while systems 2 and 3 were significantly more prevalent among isolates of hyperinvasive clonal complexes than among isolates of poorly invasive clonal complexes. In laboratory cultures, systems 1 and 2 were expressed. However, several sera from patients recovering from disseminated meningococcal disease recognized the TpsAs of systems 2 and 3, indicating the expression of these systems during infection. Furthermore, we showed that the major secreted TpsAs of systems 1 and 2 depend on their cognate TpsBs for transport across the outer membrane and that the system 1 TpsAs undergo processing. Together, our data indicate that TPS systems may contribute to the virulence of N. meningitidis.
Published ahead of print on 4 August 2008.
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