Abstract
Burkholderia pseudomallei infection causes melioidosis, which is often fatal if untreated. There is a need to develop new and more effective treatments for melioidosis. This study reports apo and cofactor-bound crystal structures of the potential drug target betaine aldehyde dehydrogenase (BADH) from B.pseudomallei. A structural comparison identified similarities to BADH from Pseudomonas aeruginosa which is inhibited by the drug disulfiram. This preliminary analysis could facilitate drug-repurposing studies for B. pseudomallei.
Highlights
Burkholderia pseudomallei is a rod-shaped, motile, flagellated, soil-dwelling Gram-negative proteobacterium of the Burkholderiaceae family that thrives in tropical and subtropical regions (Gassiep et al, 2021)
betaine aldehyde dehydrogenase (BADH) catalyzes the irreversible oxidation of betaine aldehyde to the osmoprotectant betaine and is being investigated as a drug target for drug-resistant bacteria, notably Pseudomonas aeruginosa, because its inhibition blocks choline catabolism and leads to the accumulation of the highly toxic betaine aldehyde (Gonzalez-Segura et al, 2009)
BpBADH-His was purified using a two-step protocol consisting of an immobilized metal-affinity chromatography (IMAC) step and size-exclusion chromatography (SEC)
Summary
Burkholderia pseudomallei is a rod-shaped, motile, flagellated, soil-dwelling Gram-negative proteobacterium of the Burkholderiaceae family that thrives in tropical and subtropical regions (Gassiep et al, 2021). B. pseudomallei causes melioidosis, a deadly emerging opportunistic infection mainly of the immunocompromised (Hall et al, 2019; Poe et al, 1971; Veluthat et al, 2021). Melioidosis is endemic in South Asia and Northern Australia, with $165 000 cases annually; the global distribution of B. pseudomallei is unknown, as the associated disease is underreported and misdiagnosed (Patil et al, 2016; Poe et al, 1971; Veluthat et al, 2021). BADH catalyzes the irreversible oxidation of betaine aldehyde to the osmoprotectant betaine and is being investigated as a drug target for drug-resistant bacteria, notably Pseudomonas aeruginosa, because its inhibition blocks choline catabolism and leads to the accumulation of the highly toxic betaine aldehyde (Gonzalez-Segura et al, 2009)
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