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Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria

Nature Biotechnology volume 18, pages 1060–1064 (2000)Cite this article

Abstract

Two recombinant strains of Streptococcus gordonii, secreting or displaying a microbicidal single-chain antibody (H6), and stably colonizing rat vagina, were used to treat an experimental vaginitis caused by Candida albicans. A post-challenge intravaginal delivery of the H6-secreting strain was as efficacious as fluconazole in rapidly abating the fungal burden. Three weeks after challenge, 75% and 37.5% of the rats treated with the H6-secreting or displaying bacteria, respectively, were cured of the infection, which persisted in 100% of the animals treated with a S. gordonii strain expressing an irrelevant single-chain antibody. Thus, a human commensal bacterium can be suitably engineered to locally release a therapeutic antibody fragment.

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Figure 1: Western blot analysis of recombinant S. gordonii strains expressing M6-H6 fusion proteins.
Figure 2: In vitro killing of Candida albicans by Streptococcus gordonii displaying scFvH6 on the surface.
Figure 3: Outcome of vaginal infection in rats infected with Candida albicans (day 0) and untreated or treated with Streptococcus gordonii strains (109 cells in 0.1 ml of each strain) or fluconazole (100 μg) as indicated, on days 0 (1 h post infection), 1, and 2 post infection (arrows).

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Acknowledgements

This work was supported by grants from the Commission of the European Union (fifth frame work contract QLK2-1999-00854) to MRO; from CNR (P. F. Biotecnologie, contract no. 97.01185.PF49) to GP and GT; from the Progetto Nazionale AIDS 1998 (contract no. 50B.32) to LP, and from the Progetto Nazionale AIDS 1998 (contract no. 50C/B) to AC.

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Authors and Affiliations

  1. Dipartimento di Biologia Molecolare/Microbiologia, Università degli Studi di Siena, Siena, Italy

    Concetta Beninati, Marco Rinaldo Oggioni, Maria Rita Spinosa, Tiziana Maggi & Gianni Pozzi

  2. Istituto di Microbiologia e Università degli Studi di Messina, Messina, Italy

    Concetta Beninati & Giuseppe Teti

  3. Laboratorio di Batteriologia e Micologia Medica, Istituto Superiore di Sanità, Roma, Italy

    Maria Boccanera, Flavia De Bernardis & Antonio Cassone

  4. Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia, Università degli Studi di Parma, Parma, Italy

    Stefania Conti, Walter Magliani & Luciano Polonelli

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  1. Concetta Beninati
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Correspondence to Luciano Polonelli.

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Beninati, C., Oggioni, M., Boccanera, M. et al. Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria. Nat Biotechnol 18, 1060–1064 (2000). https://doi.org/10.1038/80250

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