Hospital-acquired infections (HAI) are a major problem in American healthcare. Bacterial and viral infections persist, despite very aggressive mechanical treatment. Why is disinfection so difficult? Two recent papers address this topic (Herman-Bausier, P.; Dufrêne, Y.F. et al. Force matters in hospital-acquired infections. Science, 30 Mar 2018, 359[6383], 1464–5 and Milles, L.F.; Schulten, K. et. al. Molecular mechanism of extreme mechanostability in a pathogen adhesin. Science 30 Mar 2018, 359[6383], 1527–33). The first article explains the relevancy of the primary reference (Milles et al.).
Infected biofilms are responsible for many HAIs. Conventional methods studying molecular interactions do not explain the unusual stability of microbe-infected biofilms. However, Milles et. al. used an atomic force microscope (AFM) to measure the force required to remove a staphylococcus bacterium from a surface coated with fibrinogen. They found that the rupture force was about 2 nanonewtons. This is similar to the strength of covalent bonds, and much stronger than most intermolecular or interparticle interactions.
In more detail, Milles and team used an AFM to measure the strength of the adhesin SD-repeat protein G (SdrG)-fibrinogen (Fg) complex. They propose that the SdrG binds to Fg with an allosteric mechanism involving N2 and N3 subdomains of SdrG bind to peptide sequences in the Fg molecule. This was done with immobilizing SdrG on the AFM tip and the N2 and N3 ligands on the substrate. The researchers proposed a “dock, lock, and latch” mechanism. Rupture of the SdrG-FG complex requires that all bonds, including many hydrogen bonds, rupture simultaneously. Studies with other bacteria produced similar results, suggesting that this type of binding is more general.
After thinking about this for a bit, it seems possible that the immobilized bacterium can replicate and form a stable colony on the surface. This colony would probably show normal microbe–microbe bonding, which is probably much weaker than the SdrG-FG complex. If this colony is exposed to the patient, part of it could break off and transfer, and thus infect the patient.
Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected]
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