AUTHOR=Gomes Priscila S. F. C. , Forrester Meredith , Pace Margaret , Gomes Diego E. B. , Bernardi Rafael C. 

TITLE=May the force be with you: The role of hyper-mechanostability of the bone sialoprotein binding protein during early stages of Staphylococci infections

JOURNAL=Frontiers in Chemistry

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1107427

DOI=10.3389/fchem.2023.1107427

ISSN=2296-2646

ABSTRACT=<p>The bone sialoprotein-binding protein (Bbp) is a mechanoactive MSCRAMM protein expressed on the surface of <italic>Staphylococcus aureus</italic> that mediates adherence of the bacterium to fibrinogen-<italic>α</italic> (Fg<italic>α</italic>), a component of the bone and dentine extracellular matrix of the host cell. Mechanoactive proteins like Bbp have key roles in several physiological and pathological processes. Particularly, the Bbp: Fg<italic>α</italic> interaction is important in the formation of biofilms, an important virulence factor of pathogenic bacteria. Here, we investigated the mechanostability of the Bbp: Fg<italic>α</italic> complex using <italic>in silico</italic> single-molecule force spectroscopy (SMFS), in an approach that combines results from all-atom and coarse-grained steered molecular dynamics (SMD) simulations. Our results show that Bbp is the most mechanostable MSCRAMM investigated thus far, reaching rupture forces beyond the 2 nN range in typical experimental SMFS pulling rates. Our results show that high force-loads, which are common during initial stages of bacterial infection, stabilize the interconnection between the protein’s amino acids, making the protein more “rigid”. Our data offer new insights that are crucial on the development of novel anti-adhesion strategies.</p>