Meningococcal Two-Partner Secretion Systems and Their Association with Outcome in Patients with Meningitis

Author:

Piet Jurgen R.12,van Ulsen Peter3,ur Rahman Sadeeq3,Bovenkerk Sandra2,Bentley Stephen D.4,van de Beek Diederik1,van der Ende Arie25

Affiliation:

1. Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center (AMC), Amsterdam, the Netherlands

2. Department of Medical Microbiology, Academic Medical Center (AMC), Amsterdam, the Netherlands

3. Section of Molecular Microbiology, Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, the Netherlands

4. Wellcome Trust Sanger Institute, Hinxton, United Kingdom

5. The Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center (AMC), Amsterdam, the Netherlands

Abstract

ABSTRACT Two-partner secretion (TPS) systems export large TpsA proteins to the surface and extracellular milieu. In meningococci, three different TPS systems exist, and of these, TPS system 2 (TPS2) and TPS3 can be detected by the host's immune system. We evaluated the distribution of TPS systems among clinical isolates from two prospective cohort studies comprising 373 patients with meningococcal meningitis. TPS system 1 was present in 91% of isolates, and system 2 and/or 3 was present in 67%. The TPS system distribution was related to clonal complexes. Infection with strains with TPS2 and/or TPS3 resulted in less severe disease and better outcomes than infection with strains without these systems. Using whole-blood stimulation experiments, we found no differences in the host cytokine response between patients infected with TPS system 2 and 3 knockout strains and patients infected with a wild-type strain. In conclusion, meningococcal TPS system 2 and/or 3 is associated with disease severity and outcome in patients with meningitis.

Funder

Netherlands Organization for Health Research and Development

Academic Medical Center

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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