Outer membrane vesicle-mediated serum protection inAggregatibacter actinomycetemcomitans

Abstract

Aggregatibacter actinomycetemcomitans belongs to the HACEK group of fastidious Gramnegative 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 serumsensitive 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.

Sphingolipid-Containing Outer Membrane Vesicles Serve as a Delivery Vehicle To Limit Macrophage Immune Response to Porphyromonas gingivalis

“…Locally, one of the characteristics of sites affected by periodontitis is the increase of Gram-negative anaerobes, such as Porphyromonas gingivalis , Tannerella forsythia , and Treponema denticola , that are abundant in specific virulence factors, including gingipains, lipopolysaccharide, capsular polysaccharide, lipoproteins, and other molecules ( 9 , 10 ). Interestingly, several bacteria associated with periodontal disease, including P. gingivalis , are known OMV producers ( 6 , 11 , 12 ).…”

Aggregatibacter actinomycetemcomitans and Filifactor alocis: Two exotoxin-producing oral pathogens

“…This supports the role of OMVs as triggers of innate immunity. A. actinomycetemcomitans OMVs can bind to the classical and mannose-binding lectin (MBL) complement inhibitor, C4-binding protein, by means of the outer membrane protein A1 (OmpA1) [ 52 ], which is consistent with an ability of the vesicles to mediate serum protection in vitro [ 53 ]. The mechanism(s) of how A. actinomycetemcomitans OMVs enter and/or delivers cargo into host cells is not entirely clear.…”

“…OMVs appear to play a significant role in the ability of A. actinomycetemcomitans to evade complement attack. These vesicles serve as a decoy that triggers complement activation through lipopolysaccharide (LPS) and takes in complement components [ 53 ]. In turn, LPS of some A. actinomycetemcomitans strains (i.e., strain Y4) can bind strongly to C3b, blocking the interaction between complement-derived opsonins with LPS decreasing neutrophils complement-dependent response [ 59 ].…”

Membrane vesicles from periodontal pathogens and their potential roles in periodontal disease and systemic illnesses

“…68 Analogously, A. actinomycetemcomitans OMVs safeguarded susceptible bacteria in host serum by being baits to activate the complement system and consume its components. 69 4.1.4 | Advantages over the whole bacteria Surprisingly, the effects of OMVs are sometimes more stunning than the bacteria themselves. P. gingivalis OMVs are fairly invasive, since the number of epithelial cells and fibroblasts with internalized P. gingivalis OMVs doubled that with intercellular P. gingivalis.…”