Secretion systems shaping host–pathogen interactions in Burkholderia species

Understanding the virulence mechanisms of pathogenic bacteria is crucial for elucidating their ability to cause disease. Among these, type secretion systems (TSS) are important for mediating host-pathogen interactions. This review focuses on the TSS in Burkholderia species, emphasizing their molecular structures, mechanisms, and their role in virulence. Burkholderia spp. employ a variety of TSS, each contributing distinctly to pathogenicity. Type 1 SS (T1SS) facilitate the export of toxins/enzymes to the extracellular space, promoting host-tissue damage and immune modulation. T2SS secretes hydrolytic enzymes that breach the host barriers. T3SS injects the effectors directly into the host cell, thereby aiding intracellular bacterial survival. T4SS translocates proteins and DNA, disrupting the host immune defenses and delaying vacuolar maturation. T5SS autotransporters mediate adhesion, invasion, and intracellular mobility through actin polymerization. T6SS targets both host and competing microbes through delivering toxic effectors, aiding in immune evasion, competition, and replication. Comparatively, T7SS-T11SS are discussed to provide a broader bacterial context as these TSSs are not established in Burkholderia spp. currently. This review uniquely integrates the structural, functional, and synergistic roles of all major secretion systems (Types 1-6) in Burkholderia spp., highlighting how their coordinated actions collectively shape host-pathogen interactions and drive virulence. KEY POINTS: • Burkholderia spp. exploit diverse secretion systems to manipulate host cells to enable their intracellular survival and immune evasion. • This review uniquely integrates secretion systems with host actin remodeling, outer membrane vesicles, biofilm formation, and antimicrobial resistance to present a systems-level view of Burkholderia-associated infection pathogenesis. • We highlight emerging diagnostic, therapeutic, and vaccine-relevant targets to address Burkholderia spp. infections and advance global health goals (Sustainable Development Goal 3).