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The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia.

ABSTRACT: A complement-independent bactericidal IgG1 against the OspB of Borrelia burgdorferi increased the permeability of the outer membrane through the creation of openings of 2.8 - 4.4 nm, resulting in its osmotic lysis. Cryo-electron microscopy and tomography demonstrated that exposure to the antibody causes the formation of outer membrane projections and large breaks which may precede the increase in permeability of the outer membrane. The bactericidal effect of this antibody is not transferable to Escherichia coli expressing rOspB on its outer membrane. Additionally, the porin P66, the only protein that coprecipitated with OspB, is dispensable for the bactericidal mechanism.

SUBMITTER: LaRocca TJ

PROVIDER: S-EPMC2705580 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia.

LaRocca Timothy J TJ Holthausen David J DJ Hsieh Chyongere C Renken Christian C Mannella Carmen A CA Benach Jorge L JL

Proceedings of the National Academy of Sciences of the United States of America 20090619 26

A complement-independent bactericidal IgG1 against the OspB of Borrelia burgdorferi increased the permeability of the outer membrane through the creation of openings of 2.8 - 4.4 nm, resulting in its osmotic lysis. Cryo-electron microscopy and tomography demonstrated that exposure to the antibody causes the formation of outer membrane projections and large breaks which may precede the increase in permeability of the outer membrane. The bactericidal effect of this antibody is not transferable to ...[more]

PMID: 19549817

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Project description:Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT) was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1(+) cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2?years). Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate over a 1-year period (hazard ratio: 2.83). In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration of immunosuppressive treatments, robust ADCC responsiveness can be maintained in some KTRs. Because it evaluates both the Fab recognition of alloantigens and Fc-driven NK cell activation, the NK-CHAT represents a potentially valuable tool for the non-invasive and individualized evaluation of humoral risk during transplantation.

Dataset Information

The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia.

Publications

The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia.

Similar Datasets

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