Molecular mechanism of extreme mechanostability in a pathogen adhesin

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Science  30 Mar 2018:
Vol. 359, Issue 6383, pp. 1527-1533
DOI: 10.1126/science.aar2094

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How a pathogen holds on to its host

Staphylococcus epidermidis and Staphylococcus aureus are pathogens that can form biofilms on implants and medical devices. Central to biofilm formation is a very tight interaction between microbial surface proteins called adhesins and components of the extracellular matrix of the host. Milles et al. used atomic force microscopy-based single-molecule force spectroscopy combined with steered molecular dynamics to explore how the bond between staphylococcal adhesin SdrG and its target fibrinogen peptide can withstand forces greater than 2 nanonewtons (see the Perspective by Herman-Bausier and Dufrêne). The peptide is confined in a coiled geometry in a deep and rigid pocket through hydrogen bonds between SdrG and the peptide backbone. If pulled, the load is distributed over all hydrogen bonds so that all bonds must be broken at once to break the interaction.

Science, this issue p. 1527; see also p. 1464


High resilience to mechanical stress is key when pathogens adhere to their target and initiate infection. Using atomic force microscopy–based single-molecule force spectroscopy, we explored the mechanical stability of the prototypical staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen β. Steered molecular dynamics simulations revealed, and single-molecule force spectroscopy experiments confirmed, the mechanism by which this complex withstands forces of over 2 nanonewtons, a regime previously associated with the strength of a covalent bond. The target peptide, confined in a screwlike manner in the binding pocket of SdrG, distributes forces mainly toward the peptide backbone through an intricate hydrogen bond network. Thus, these adhesins can attach to their target with exceptionally resilient mechanostability, virtually independent of peptide side chains.

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