6hhu | pdb_00006hhu
Structure of the Bacillus anthracis Sap S-layer assembly domain
Structural highlights
Function[SLAP1_BACAN] The S-layer is a paracrystalline mono-layered assembly of proteins which coat the surface of bacteria. Publication Abstract from PubMedAnthrax is an ancient and deadly disease caused by the spore-forming bacterial pathogen Bacillus anthracis. At present, anthrax mostly affects wildlife and livestock, although it remains a concern for human public health-primarily for people who handle contaminated animal products and as a bioterrorism threat due to the high resilience of spores, a high fatality rate of cases and the lack of a civilian vaccination programme(1,2). The cell surface of B. anthracis is covered by a protective paracrystalline monolayer-known as surface layer or S-layer-that is composed of the S-layer proteins Sap or EA1. Here, we generate nanobodies to inhibit the self-assembly of Sap, determine the structure of the Sap S-layer assembly domain (Sap(AD)) and show that the disintegration of the S-layer attenuates the growth of B. anthracis and the pathology of anthrax in vivo. Sap(AD) comprises six beta-sandwich domains that fold and support the formation of S-layers independently of calcium. Sap-inhibitory nanobodies prevented the assembly of Sap and depolymerized existing Sap S-layers in vitro. In vivo, nanobody-mediated disruption of the Sap S-layer resulted in severe morphological defects and attenuated bacterial growth. Subcutaneous delivery of Sap inhibitory nanobodies cleared B. anthracis infection and prevented lethality in a mouse model of anthrax disease. These findings highlight disruption of S-layer integrity as a mechanism that has therapeutic potential in S-layer-carrying pathogens. Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax.,Fioravanti A, Van Hauwermeiren F, Van der Verren SE, Jonckheere W, Goncalves A, Pardon E, Steyaert J, De Greve H, Lamkanfi M, Remaut H Nat Microbiol. 2019 Jul 15. pii: 10.1038/s41564-019-0499-1. doi:, 10.1038/s41564-019-0499-1. PMID:31308522[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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