While bioengineers ask how the shape of diagnostic and therapeutic particles impacts their pharmacological efficiency, biodistribution, and toxicity, microbiologists suggested that morphological adaptations enable pathogens to perhaps evade the immune response. Here, a shape-dependent process is described that limits phagocytosis of filamentous Escherichia coli bacteria by macrophages: successful uptake requires access to one of the terminal bacterial filament poles. By exploiting micropatterned surfaces, we further demonstrate that microenvironmental heterogeneities can slow or inhibit phagocytosis. A comparison to existing literature reveals a common shape-controlled uptake mechanism for both high-aspect ratio filamentous bacteria and engineered particles.
To clear pathogens from host tissues or biomaterial surfaces, phagocytes have to break the adhesive bacteria-substrate interactions. Here we analysed the mechanobiological process that enables macrophages to lift-off and phagocytose surface-bound Escherichia coli (E. coli). In this opsonin-independent process, macrophage filopodia hold on to the E. coli fimbriae long enough to induce a local protrusion of a lamellipodium. Specific contacts between the macrophage and E. coli are formed via the glycoprotein CD48 on filopodia and the adhesin FimH on type 1 fimbriae (hook). We show that bacterial detachment from surfaces occurrs after a lamellipodium has protruded underneath the bacterium (shovel), thereby breaking the multiple bacterium-surface interactions. After lift-off, the bacterium is engulfed by a phagocytic cup. Force activated catch bonds enable the long-term survival of the filopodium-fimbrium interactions while soluble mannose inhibitors and CD48 antibodies suppress the contact formation and thereby inhibit subsequent E. coli phagocytosis.
Surface fouling, i.e. the non-specific surface adhesion of proteins, bacteria and higher organisms, poses a severe problem in many areas ranging from modern diagnostic and therapeutic medical devices to food processing and food wrapping technology to corrosion prevention and
marine technology. One approach to address these problems is to coat surfaces with nonfouling polymers. The properties of a new class of nonfouling polymer coatings made from poly(2-methyl-2-oxazoline) (PMOXA) were investigated here in comparison with the most frequently used polymer in this
context, poly(ethylene glycol) (PEG). Both polymers were side-chain grafted onto a polycationic poly-L-lysine (PLL) backbone. The PMOXA graft copolymers spontaneously self-assembled to form monolayers on negatively charged surfaces. PMOXA surface coatings were as efficient as PEG-based coatings
in suppressing protein and bacterial adsorption. The minimal number of side chain monomer units per surface area that are needed to obtain fully resistant surfaces was lower though for PMOXA than for PEG graft copolymers as a result of the higher molecular weight of the PMOXA monomer unit.
and Burkovski, Andreas (2019) Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae. Vaccine, 37 (23). pp. 3061-3070.
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