Bacterial Surfaces and Barriers: Biogenesis and Pathogen-Host Interactions

The bacterial surface represents the primary interface between pathogens and hosts, yet its chemical and architectural complexity challenges conventional classification. This Review examines structural organization, molecular composition, and biogenesis of bacterial surface components across the Gracilicutes and Terrabacteria clades, linking mechanistic detail to pathogenic function. We describe lipid diversity, integral membrane protein biogenesis, and lipoprotein processing at the inner membrane and how these components support surface remodeling, secretion, and virulence. We then examine the peptidoglycan layer and its role in immune recognition and surface protein display, teichoic acids and their contributions to antimicrobial resistance and immune evasion, and S layers, whose crystalline arrays mediate adhesion and immune modulation. The outer membrane section covers lipopolysaccharide biosynthesis, outer membrane protein biogenesis and folding, lipoprotein trafficking, and contributions to pathogenicity, while the mycobacterial section addresses the mycolyl-arabinogalactan-peptidoglycan complex and virulence factors. We discuss bacterial capsule diversity, biosynthesis, and use as vaccine antigens, along with adhesive surface structures such as fimbriae, pili, and curli fibers and their roles in colonization and biofilm formation, before covering secretion systems types I through XI and their contributions to virulence. This Review provides a framework for understanding how bacterial surface diversity shapes infection and identifies chemical vulnerabilities for therapeutics.