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A bacteriolytic agent that detects and kills Bacillus anthracis

Nature volume 418, pages 884–889 (2002)Cite this article

Abstract

The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction1,2. Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic-resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploited the inherent binding specificity and lytic action of bacteriophage enzymes called lysins for the rapid detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated from the γ phage of B. anthracis, specifically kills B. anthracis isolates and other members of the B. anthracis ‘cluster’ of bacilli in vitro and in vivo. Both vegetative cells and germinating spores are susceptible. The lytic specificity of PlyG was also exploited as part of a rapid method for the identification of B. anthracis. We conclude that PlyG is a tool for the treatment and detection of B. anthracis.

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Figure 1: Characterization of PlyG.
Figure 2: The specific and rapid killing action of PlyG.
Figure 3: PlyG causes profound morphological changes in, and ultimately lysis of, RSVF1.
Figure 4: Survival of PlyG-treated BALB/c mice infected with RSVF1.
Figure 5: PlyG-mediated spore killing and detection.

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Acknowledgements

We thank P. J. Piggot, L. W. Mayer, A. L. Turetsky, A. Aronson, A. Keynan, H.-W. Ackerman, R. J. McNall and T. A. Kokjohn for their gifts of strains; E. Sphicas at the Bio-imaging Resource Center at The Rockefeller University for help with electron microscopy; R. L. Russell and S. Zhu for technical help; New Horizons Diagnostics for their luminometer and reagents and P. Model and members of the V.A.F. laboratory for reviewing this manuscript. We also thank A. Keynan for reviewing this manuscript and for advice regarding spore preparation and germination. This work was supported by a grant from the Defense Advanced Research Projects Agency (DARPA).

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Author notes

  1. Vincent A. Fischetti: Correspondence and requests for materials should be addressed to V.A.F. The γ phage plyG sequence has been deposited in GenBank (accession number AF536823).

Authors and Affiliations

  1. Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, 10021, USA

    Raymond Schuch, Daniel Nelson & Vincent A. Fischetti

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Schuch, R., Nelson, D. & Fischetti, V. A bacteriolytic agent that detects and kills Bacillus anthracis. Nature 418, 884–889 (2002). https://doi.org/10.1038/nature01026

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