Proteomics of Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles.

Jens Kreth,Thomas Kieselbach,Elisabeth Granström,Vincent Zijnge,Jan Oscarsson

doi:10.1371/journal.pone.0138591

Jens Kreth, Thomas Kieselbach + Show 3 more

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https://doi.org/10.1371/journal.pone.0138591

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Journal: PloS one	Publication Date: Sep 18, 2015
Citations: 108	License type: CC BY 4.0

Affiliation: Umeå University, University Medical Center Groningen

Abstract

Aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. Outer membrane vesicles (OMVs) released by this species have been demonstrated to deliver effector proteins such as cytolethal distending toxin (CDT) and leukotoxin (LtxA) into human host cells and to act as triggers of innate immunity upon carriage of NOD1- and NOD2-active pathogen-associated molecular patterns (PAMPs). To improve our understanding of the pathogenicity-associated functions that A. actinomycetemcomitans exports via OMVs, we studied the proteome of density gradient-purified OMVs from a rough-colony type clinical isolate, strain 173 (serotype e) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This analysis yielded the identification of 151 proteins, which were found in at least three out of four independent experiments. Data are available via ProteomeXchange with identifier PXD002509. Through this study, we not only confirmed the vesicle-associated release of LtxA, and the presence of proteins, which are known to act as immunoreactive antigens in the human host, but we also identified numerous additional putative virulence-related proteins in the A. actinomycetemcomitans OMV proteome. The known and putative functions of these proteins include immune evasion, drug targeting, and iron/nutrient acquisition. In summary, our findings are consistent with an OMV-associated proteome that exhibits several offensive and defensive functions, and they provide a comprehensive basis to further disclose roles of A. actinomycetemcomitans OMVs in periodontal and systemic disease.

Highlights

Periodontal diseases are characterized by chronic inflammation of the gingiva, and progressive destruction of alveolar bone and supporting tissues around the teeth resulting in tooth loss [1]
We note that cytolethal distending toxin (CDT) was not identified in the strain 173 Outer membrane vesicles (OMVs) proteome, whereas this toxin is released in association with vesicles by a number of other A. actinomycetemcomitans strains of serotypes a, b, and c [36]
We have characterized the OMV-associated proteome of the rough A. actinomycetemcomitans serotype e strain, 173 by LC-MS/MS, and used manual literature search and the VirulentPred algorithm to assess the virulence potential of this subproteome

Summary

Introduction

Periodontal diseases are characterized by chronic inflammation of the gingiva, and progressive destruction of alveolar bone and supporting tissues around the teeth resulting in tooth loss [1]. Colonization by the Gram-negative human pathogen Aggregatibacter actinomycetemcomitans is strongly associated with aggressive forms of periodontitis in adolescents and young adults [2, 3], and the organism is a systemic pathogen, associated with non-oral infections such as endocarditis [4]. Proteomics of A. actinomycetemcomitans OMVs design, data collection and analysis, decision to publish, or preparation of the manuscript

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Results

Conclusion