Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a Mucosal Immune Response

Abstract

We previously reported that mutation of galE in Porphyromonas gingivalis has pleiotropic effects, including a truncated lipopolysaccharide (LPS) O-antigen and deglycosylation of the outer membrane protein OMP85 homolog. In the present study, further analysis of the galE mutant revealed that it produced little or no outer membrane vesicles (OMVs). Using three mouse antisera raised against whole cells of the P. gingivalis wild type strain, we performed ELISAs to examine the reactivity of these antisera with whole cells of the wild type or the galE mutant. All three antisera had significantly lower reactivity against the galE mutant compared to wild type. OMVs, but not LPS, retained the immunodominant determinant of P. gingivalis, as determined by ELISAs (with wild type LPS or OMVs as antigen) and absorption assays. In addition, we assessed the capacity of OMVs as a vaccine antigen by intranasal immunization to BALB/c mice. Synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [Poly (I∶C)], an agonist of Toll-like receptor 3 (TLR3), was used as the mucosal adjuvant. Vaccination with OMV elicited dramatically high levels of P. gingivalis-specific IgA in nasal washes and saliva, as well as serum IgG and IgA. In conclusion, the OMVs of P. gingivalis have an important role in mucosal immunogenicity as well as in antigenicity. We propose that P. gingivalis OMV is an intriguing immunogen for development of a periodontal disease vaccine.

Rotation of Vibrio fischeri Flagella Produces Outer Membrane Vesicles That Induce Host Development

“…In several bacterial genera, such as Klebsiella and Porphyromonas, mutations that modify the O antigen have been reported to affect OMVs by altering the protein content and reducing OMV production, respectively (41,42). Similarly, while Pseudomonas O-antigen mutants have no effect on the rate of OMV release, they do affect both their contents and size (43).…”

Prokaryotic membrane vesicles: new insights on biogenesis and biological roles

“…Cif is delivered into host cells after OMV fusion with lipid rafts where it inhibits the deubiquitination of CFTR leading to its lysosomal degradation (Bomberger et al, 2009(Bomberger et al, , 2011. Different groups demonstrated the ability of OMVs from different bacteria to activate the immune system in various ways Vidakovics et al, 2010;Nakao et al, 2011;Schaar et al, 2011;Elmi et al, 2012;Lee et al, 2012;Pollak et al, 2012;Roier et al, 2012Roier et al, , 2013Jun et al, 2013;Kim et al, 2013;Deknuydt et al, 2014). Bordetella pertussis causes an increase in intracellular cAMP levels of the host cells through the delivery of its adenylate cyclase toxin as OMV cargo (Donato et al, 2012).…”

Biogenesis and Function of Porphyromonas Gingivalis Outer Membrane Vesicles

“…Besides the expression of FimA, vesiculation of P. gingivalis has been linked to the expressions of an OmpA-like protein (Pgm6/7) and galactose 4-epimerase (GalE) [26,27]. GalE is known to catalyze the interconversion between uridine diphosphate (UDP)-glucose and UDP-galactose.…”

“…GalE is known to catalyze the interconversion between uridine diphosphate (UDP)-glucose and UDP-galactose. It was reported that vesicles could not be found on either the surface of a galE mutant or in the growth media when monitored at different time points over 3 days in culture [27]. The authors felt that this could be due to the pleiotropic effects of the galE mutation on truncation of LPS O-antigen and nonglycosylated form of the outer membrane Omp85 homolog, which were also observed in the galE mutant.…”