Aantibody response to Burkholderia pseudomallei in a 13-year chronic infection: Relationship of antibody response to bacterial genomics and proteomics 2308991

Abstract

Abstract Introduction Burkholderia pseudomallei (Bp), a Gram-negative soil bacterium, causes the disease melioidosis. The majority of melioidosis cases are classified as acute disease. However, some patients present with a chronic infection (symptoms ≥2 months) or activation of infection from latency. In this study, we tracked the antibody response of a patient with a ∼ ≥ 13-year chronic infection to monitor how humoral response pressures may alter the bacterial proteome or genome. Methods We compared Bp isolates from the patient with a closely related environmental isolate from the patient’s home of the same sequence type. Isolates and patient immune responses were compared using genomic, proteomic (mass spectrometry, Western analysis), and immunological assays (Western Blot, ELISA, and nucleic acid-programmable protein array (NAPPA). Results We found that cultured strains persisting in the patient had a significant reduction in bacterial proteome. The reduction was partially correlated with a decrease in bacterial genome size. However, not all reductions were associated with gene deletion. Early patient serum samples showed that many antibodies reacted to the environmental bacterium. Both capsular polysaccharide (CPS) and lipopolysaccharide A (LPSA)-specific IgG antibodies were detected early during the patient’s infection. The reactivity peaked during early phase and then waned over the remaining monitoring period. The carbohydrate reactivity correlated with expression in patient isolates . We screened 1660 reactive Bp antigens by the NAPPA protein array and determined that 160 proteins showed reactivity and outer membrane protein reactivity increased over time after the loss of CPS and LPS antigens. Conclusion In combination, these data suggest that reduced or eliminated CPS and LPS virulence factor expression could be selected for in response to antibody selection. This antibody selection could increase immune cell availability of outer membrane proteins but were insufficient to clear Bp colonization. Funding Source Defence Threat Reduction Agency HDTRA1-22-C0013 Defence Threat Reduction Agency HDTRA1-12-C0022 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)