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Infect. Immun. doi:10.1128/IAI.00393-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Two-Partner Secretion Systems of Neisseria meningitidis Associated with Invasive Clonal Complexes

Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands; Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands; Center for Infection and Immunity Amsterdam, Department of Medical Microbiology, Academic Medical Center, 1100 DD Amsterdam, The Netherlands; Netherlands Reference Laboratory for Bacterial Meningitis (AMC/RIVM), 1100 DD Amsterdam, The Netherlands

^* To whom correspondence should be addressed. Email: peter.van.ulsen{at}falw.vu.nl.

	Abstract

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 ORFs in a collection of disease isolates. Three distinct TPS systems were identified among meningococci. System 1 is ubiquitous, while systems 2 and 3 were significantly more prevalent among isolates of hyper invasive clonal complexes than among isolates of poorly invasive clonal complexes. In laboratory cultures, systems 1 and 2 were expressed. However, several sera of patients recovering from disseminated meningococcal disease recognized the TpsAs of systems 2 and 3, indicating expression of these systems during infection. Furthermore, we show 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.