Naturally Occurring IgG Antibodies Provide Innate Protection against <b><i>Vibrio cholerae </i></b>Bacteremia by Recognition of the Outer Membrane Protein U

Abstract

Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means to verify by extracellular transcomplementation the involvement of OmpU. Our data conclusively indicate that loss, or reduced expression, of OmpU imparts resistance to V. cholerae towards serum killing. We propose that the difference in OmpU protein levels is a plausible reason for differences in serum resistance and the ability to cause bacteremia observed among V. cholerae biotypes. Our findings provide a new perspective on how naturally occurring antibodies, perhaps induced by members of the microbiome, may play a role in the recognition of pathogens and the provocation of innate immune defense against bacteremia.

Outer membrane vesicle-mediated serum protection inAggregatibacter actinomycetemcomitans

“…of A. actinomycetemcomitans OMVs is in agreement with findings with OMVs of a number of other bacterial species, i.e. M. catarrhalis, N. gonorrhoeae, P. gingivalis, and V. cholerae [30][31][32][33]. Based on previous studies with A. actinomycetemcomitans [17,21,51], we routinely determined the serum survival in 50% NHS.…”

“…This was somewhat unexpected as these OMPs were necessary for the serum resistance of strain D7SS and bound to recombinant C4-binding protein in in vitro incubations with A. actinomycetemcomitans OMVs [21]. Thus, A. actinomycetemcomitans OMVs appeared to mediate serum protection via a different mechanism than, e.g., V. cholerae OMVs, which were found to divert naturally occurring antibodies against Gramnegative organisms away from the bacterial cells via OmpU on the released vesicles [30]. Also, OMVs of M. catarrhalis and N. gonorrhoeae seemingly depended on OMPs when contributing to serum resistance [31,32].…”

“…Proteomics, and Western blot analysis of A. actinomycetemcomitans OMVs have identified several additional vesicle-associated proteins that can contribute to evasion of the immune defense, including the IL1β-binding lipoprotein, BilRI, Omp100, OmpA1, and OmpA2, and a Factor H-binding protein homologue [21,28,29]. A role of OMVs in contributing to bacterial serum resistance has been demonstrated in a number of bacterial species, including Moraxella catarrhalis, Neisseria gonorrhoeae, Porphyromonas gingivalis, and Vibrio cholerae [30][31][32][33]. Whether A. actinomycetemcomitans OMVs may also be involved in serum resistance is not known.…”

A stealth adhesion factor contributes toVibrio vulnificuspathogenicity: Flp pili play roles in host invasion, survival in the blood stream and resistance to complement activation

“…To block activation of the classical pathway, NHS was pretreated with 10 mM ethylene glycol-bis (2-aminoethylether)- N, N, N ′, N ′-tetraacetic acid and 5 mM MgCl 2 for 30 min at 37°C (EGTA/Mg 2+ ) (45). To prepare the MBL-depleted serum, mannose-agarose beads (Sigma-Aldrich) were washed three times with sterile PBS and then incubated with NHS at 4°C for 1 h with gentle rotation (46). The alternative pathway is inhibited via properdin absorption with bentonite (47).…”

Bystander Cells Taking Action

“…The same applies for the Chemistry Prize. Electron microscopy is an essential tool when studying innate immunity [6,7,8,9,10,11]. It will therefore be exciting to see how the new developments will advance the forthcoming research outcome.…”