Abstract
ABSTRACT Aggregatibacter actinomycetemcomitans belongs to the HACEK group of fastidious Gram-negative organisms, a recognized cause of infective endocarditis. A. actinomycetemcomitans is also implicated in periodontitis, with rapid progress in adolescents. We recently demonstrated that the major outer membrane protein, OmpA1 was critical for serum survival of the A. actinomycetemcomitans serotype a model strain, D7SS, and that the paralogue, OmpA2 could operate as a functional homologue to OmpA1 in mediating serum resistance. In the present work, an essentially serum-sensitive ompA1 ompA2 double mutant A. actinomycetemcomitans strain derivative was exploited to elucidate if A. actinomycetemcomitans OMVs can contribute to bacterial serum resistance. Indeed, supplementation of OMVs resulted in a dose-dependent increase of the survival of the serum-sensitive strain in incubations in 50% normal human serum (NHS). Whereas neither OmpA1 nor OmpA2 was required for the OMV-mediated serum protection, OMVs and LPS from an A. actinomycetemcomitans strain lacking the LPS O-antigen polysaccharide part were significantly impaired in protecting D7SS ompA1 ompA2. Our results using a complement system screen assay support a model where A. actinomycetemcomitans OMVs can act as a decoy, which can trigger complement activation in an LPS-dependent manner, and consume complement components to protect serum-susceptible bacterial cells.
Highlights
The HACEK group of fastidious Gram-negative organisms is an identified cause of infective endocarditis, responsible for 1.4 to 3% of cases [1]
We recently demonstrated that the major outer membrane protein, OmpA1 was critical for serum survival of the A. actinomycetemcomitans serotype a model strain, D7SS, and that the paralogue, OmpA2 could operate as a functional homologue to OmpA1 in mediating serum resistance
In order to test if outer membrane vesicles may be involved in serum resistance of A. actinomycetemcomitans, OMVs were isolated from the wild-type strain, D7SS, and from its ompA1 ompA2 double mutant derivative, as described in Materials and methods
Summary
The HACEK group of fastidious Gram-negative organisms is an identified cause of infective endocarditis, responsible for 1.4 to 3% of cases [1]. The genus Aggregatibacter is the dominant etiology of HACEK endocarditis [2]. Carriage of Aggregatibacter actinomycetemcomitans is strongly associated with periodontitis with rapid progress in adolescents and young adults [3,4,5]. A. actinomycetemcomitans is a genetically diverse species, with the serotypes a-g representing different lineages [5]. A. actinomycetemcomitans genotypes that produce high levels of leukotoxin, i.e., JP2 and cagE, respectively (serotype b) are strongly linked to periodontal attachment loss progression in North and West African adolescents [4,6]. The systemic role of A. actinomycetemcomitans, further to its involvement in endocarditis, includes its association with conditions of soft tissue abscesses, and osteomyelitis [7]. A. actinomycetemcomitans has been identified in atheromatous plaque [8] and is a candidate bacterial trigger of anti-citrulline autoimmunity in rheumatoid arthritis [9,10]
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