IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Single domain llama antibodies as specific intracellular inhibitors of SpvB, the actin ADP-ribosylating toxin of Salmonella typhimurium.
Autor/es:
ALZOGARAY V, DANQUAH W, AGUIRRE A, URRUTIA M, BERGUER P, GARCÍA VÉSCOVI E, HAAG F, KOCH-NOLTE F, GOLDBAUM FA.
Revista:
FASEB JOURNAL
Editorial:
FEDERATION AMER SOC EXP BIOL
Referencias:
Lugar: Bethesda; Año: 2011 vol. 25 p. 526 - 534
ISSN:
0892-6638
Resumen:
ADP-ribosylation of host cell proteins is a common mode of cell intoxication by pathogenic bacterial toxins. Antibodies induced by immunization with inactivated ADP-ribosylating toxins provide efficient protection in case of some secreted toxins, e.g., diphtheria and pertussis toxins. However, other ADPribosylating toxins, such as Salmonella SpvB toxin, are secreted directly from the Salmonella-containing vacuole into the cytosol of target cells via the SPI-2 encoded bacterial type III secretion system, and thus are inaccessible to conventional antibodies. Small-moleculeADP-ribosylation inhibitors are fraught with potential side effects caused by inhibition of endogenous ADPribosyltransferases. Here, we report the development of a single-domain antibody from an immunized llama that blocks the capacity of SpvB to ADP-ribosylate actinat a molar ratio of 1:1. The single-domain antibody, when expressed as an intrabody, effectively protected cells from the cytotoxic activity of a translocationcompetent chimeric C2IN-C/SpvB toxin. Transfected cells were also protected against cytoskeletal alterations induced by wild-type SpvB-expressing strains of Salmonella. This proof of principle paves the way for developingnew antidotes against intracellular toxins.