openA non-canonical, moonlighting Acinetobacter baumannii glyceraldehyde-3-phosphate dehydrogenase (GAPDH/GapA) promotes iron acquisition from heme, transferrin and lactoferrinAnjaliKumariauthorZahidGaniauthorNimmaRameshauthorShreyaGaikwadauthorAjayKumarauthorRahulDilawariauthorApurwaMahajanauthorRajesh KumarRohillaauthorSangaralingamKumaranauthorManojRajeauthorChaaya IyengarRajeauthorAcinetobacter baumannii (A. baumannii) has emerged a priority pathogen due the rapid spread of multi-drug resistant strains. Despite this, a number of metabolic pathways of this pathogen remain uncharacterized and are inferred from studies in E. coli. Whole genome analysis of clinical isolates of A. baumannii revealed the absence of several glycolytic enzymes, however, all enzymes of the Entner-Doudoroff (ED) pathway were identified, but none are characterized. Moreover, two products of this pathway i.e. glyceraldehyde-3-phosphate (G3P) and pyruvate generate deoxyxylulose 5-phosphate which is a key intermediate of Vitamin B6 synthesis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is highly conserved across species and despite sequence differences the functional enzyme is most often a �150 kDa homo-tetramer, composed of �37 kDa monomers. The present study reveals that A. baumannii expresses an unusually large enzyme of �212 kDa, with a monomer size of 53 kDa. The A. baumannii enzyme differs due to the presence of a unique N-terminal extension of 396 bp corresponding to 132 amino acids. Sequence analysis revealed that this N-terminal sequence is present across several Acinetobacter species. Our study provides the complete biochemical characterization of recombinant GapA. In addition, we identified that GapA sequesters and internalizes human transferrin (Tf), lactoferrin (Lf) and heme as an effective mechanism for iron acquisition by the pathogen. Considering its pivotal role in carbon metabolism, vitamin B6 synthesis and iron acquisition, A. baumannii GapA could significantly contribute to bacterial pathogenesis. Further, its unique structural differences may provide an opportunity for development of specific inhibitors.QR Microbiology2026-06-10Elsevier BVArticle

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