A Supramolecular Platform Technology for Bacterial Cell Surface Modification

[Image: see text] In an era of antimicrobial resistance, a better understanding of the interaction between bacteria and the sentinel immune system is needed to discover new therapeutic targets for combating bacterial infectious disease. Sentinel immune cells such as macrophages phagocytose intact bacteria and thereby initiate ensuing immune responses. The bacterial surface composition is a key element that determines the macrophage signaling. To study the role of the bacterial cell surface composition in immune recognition, we developed a platform technology for altering bacterial surfaces in a controlled manner with versatile chemical scaffolds. We show that these scaffolds are efficiently loaded onto both Gram-positive and -negative bacteria and that their presence does not impair the capacity of monocyte-derived macrophages to phagocytose bacteria and subsequently signal to other components of the immune system. We believe this technology thus presents a useful tool to study the role of bacterial cell surface composition in disease etiology and potentially in novel interventions utilizing intact bacteria for vaccination.