Bacterial protein secretion systems: Mechanisms, functions, and roles in virulence

Bacterial secretion systems are molecular nanomachines that mediate host-pathogen interactions, antibiotic resistance, and bacterial survival in diverse environments. This review offers a comprehensive overview of the major bacterial protein transport systems, including conserved export pathways (Sec and Tat) and specialized multi-component secretion machineries (type I-XI). These systems mediate the secretion of diverse substrates, such as toxins, adhesins, and enzymes, essential for bacterial virulence, immune evasion, and interbacterial competition. Special emphasis has been given to the injectisome-like secretion systems because of their effective functions in host manipulation, immune evasion, and interbacterial competition. Moreover, recently described T9SS to T11SS are addressed in detail to understand their evolutionary adaptation and biological functions. This review also discusses how environmental cues and stress responses regulate secretion systems, with special emphasis on their relevance to bacterial survival, fitness, and pathogenesis. Despite major advances, the use of multiple secretion systems and full functionality of T11SS in bacterial communities are not well understood. Elucidation of the molecular mechanisms of bacterial secretion can change the face of strategies against infections, preserving beneficial microbiota. Future research should focus on deciphering the regulatory networks controlling secretion systems, particularly the interplay between stress response pathways and secretion activity.