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Instruments / Technical Area	Publication Details	Published	Actions
I03-Macromolecular Crystallography I24-Microfocus Macromolecular Crystallography	Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax Antonella Fioravanti , Filip Van Hauwermeiren , Sander E. Van Der Verren , Wim Jonckheere , Amanda Goncalves , Els Pardon , Jan Steyaert , Henri De Greve , Mohamed Lamkanfi , Han Remaut Nature Microbiology 8 DOI: 10.1038/s41564-019-0499-1 Diamond Proposal Number(s): [12718, 17150] Show Abstract ▼ Abstract: Anthrax 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. 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 (SapAD) and show that the disintegration of the S-layer attenuates the growth of B. anthracis and the pathology of anthrax in vivo. SapAD comprises six β-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.	Jul 2019

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I03-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography

Structure of S-layer protein Sap reveals a mechanism for therapeutic intervention in anthrax

Antonella Fioravanti , Filip Van Hauwermeiren , Sander E. Van Der Verren , Wim Jonckheere , Amanda Goncalves , Els Pardon , Jan Steyaert , Henri De Greve , Mohamed Lamkanfi , Han Remaut

Nature Microbiology 8

DOI: 10.1038/s41564-019-0499-1

Diamond Proposal Number(s): [12718, 17150]

Show Abstract ▼

Jul 2019