A plasma proteomic diagnostic for melioidosis

PROJECT SUMMARY Melioidosis is a tropical infection caused by inoculation, inhalation, or ingestion of the Gram-negative soil saprophyte and Tier 1 select agent Burkholderia pseudomallei (Bps). The overall melioidosis mortality rate exceeds 40% in endemic areas of southeast Asia such as northeastern Thailand (despite appropriate treatment), and modeling indicates that 165,000 cases of human melioidosis occur annually worldwide. For decades, diagnosis of melioidosis has required culture of Bps from a clinical specimen. This may take several days, delaying appropriate treatment, and in many resource-limited settings the necessary microbiology facilities for bacterial culture and identification are not available. Few suitable non-culture-based diagnostics exist. Performing a case-control analysis nested within a prospective, single-center cohort study of patients hospitalized with infection (Ubon-Sepsis study), we have developed an eight-protein signature in plasma that, in preliminary studies, has high accuracy differentiating melioidosis from other causes of infection. These results suggest that measuring a limited number of circulating proteins during initial presentation has significant diagnostic potential for melioidosis. Our central hypothesis is that this proteomic signature is a novel and accurate diagnostic tool in identifying patients with melioidosis. To test this potentially high impact hypothesis, we will leverage our singular expertise in melioidosis proteomics, human immunology, and access to independent Thai and Australian cohorts of melioidosis patients in the following specific aims: 1) Externally validate the diagnostic accuracy of the eight-protein aptamer-based signature for the detection of melioidosis in two geographically independent prospective studies. 2) Confirm the diagnostic accuracy of the aptamer- derived proteomic classifier for melioidosis using orthogonal immunoassays. If our hypotheses are proven, the use of blood proteins as a melioidosis diagnostic could significantly enhance our present approaches to identifying melioidosis. Subsequent development of this tool for clinical use could have a beneficial impact on the burden of this often-lethal infectious disease.