Abstract: Gram-positive pathogens can colonize on mucosal tissues stably withstanding large mechanical disturbance from coughing and sneezing by secreting special surface adhesion proteins. However, how these proteins resist mechanical unfolding remains unknown. In a recent work, using single molecule force spectroscopy, Cao et al. discovered that an ester bond containing surface adhesion protein from Gram-positive bacteria, Clostridium perfringenes, remains folded even under stretching forces of >2 nN, more stable than most proteins investigated to date. Such an outstanding mechanical stability is due to the coupling between ester bond and protein topologic structure and can be dynamically regulated by surrounding conditions. This work has been published in Nature Communications and can be reached at https://doi.org/10.1038/s41467-021-25425-6.