Host-Pathogen Interactions in Melioidosis - Project Summary - Overall Burkholderia pseudomallei (Bpm), the causative agent of melioidosis, is an environmental pathogen with growing importance to global and U.S. public health. Endemic in Southeast Asia and Northern Australia, Bpm has also been identified in the continental United States, the Caribbean, and Central and South America, increasing the risk of domestic exposure through environmental emergence, international travel, and global commerce. An estimated 165,000 people develop melioidosis annually, resulting in approximately 89,000 deaths worldwide. Bpm causes diverse clinical manifestations, exhibits intrinsic resistance to multiple antibiotics, and is associated with recurrent infection. Inhalation is the most efficient route of infection, with pulmonary disease frequently progressing to septicemia and death, particularly following infection with highly virulent strains. This project will define the mechanisms responsible for pulmonary melioidosis by identifying bacterial virulence determinants required for lung infection, dissemination, and immune modulation, while characterizing host immune pathways associated with disease severity and outcomes. Studies conducted in endemic regions provide essential access to clinically relevant isolates, well-characterized patient cohorts, and pathogen diversity unavailable elsewhere, enabling rigorous investigation of naturally occurring disease. Having access to the genomic analysis of over 1,300 Bpm isolates will highlight the role of lineage-specific genes in disease progression and mortality. Integrating bacterial pathogenesis, immunology, genomics, and translational research will identify therapeutic targets, inform diagnostics and vaccines, and strengthen U.S. preparedness against this high-consequence pathogen by advancing evidence-based strategies to prevent severe disease and reduce mortality.
