Evolutionary plasticity of bacterial surface layer protein exoskeletons

All cellular life possesses environmental interfaces like cell membranes or cell walls, yet the compositional complexity of these major cell components limits structural and evolutionary studies. Prokaryotic surface layer (S-layer) exoskeletons, with their homopolymer paracrystalline architecture, offer a more tractable evolutionary model of an environmental interface. In this study, we reveal the functional, structural and evolutionary diversity of S-layers in Gram-positive Peptostreptococcaceae, including pathogens and cancer-promoting species. We uncover novel S-layer architectures with diverse biochemical and physiological properties, enabled by a modular design co-evolving with other cell envelope components. We elucidate the mechanisms and evolutionary pathways underpinning the emergence of novel S-layers and the diversification of existing ones. Our findings establish the S-layer as a paradigm of cellular and molecular modularity and evolutionary plasticity. The demonstrated adaptability of these biological exoskeletons enables rapid reconfiguration of bacterial cell surface architecture and physiology, facilitating immune evasion in pathogens.