Metabolic acidification–linked outer membrane vesiculation in Acinetobacter baumannii

Outer membrane vesicles (OMVs) contribute to bacterial adaptation and persistence, yet the metabolic triggers of vesiculation remain poorly understood. Here, we show that clinical Acinetobacter baumannii strains vary in their capacity for glucose oxidation, with only oxidation-positive strains exhibiting acidification and enhanced OMV biogenesis. Comparative genomics revealed variable distributions of pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase homologs among isolates. In strain NCCP 16011, glucose supplementation induced acidification, biofilm formation, membrane remodeling, and enhanced OMV production. Introduction of the PQQ biosynthetic gene cluster into PQQ-deficient ATCC 17978 conferred glucose-dependent acidification and increased vesiculation. Electron microscopy and fluorescence recovery after photobleaching analyses revealed periplasmic expansion, protein accumulation, and reduced protein mobility, consistent with envelope stress. The adhesin Ata and the β-lactamase Bla OXA-51 were enriched in glucose-induced OMVs, consistent with their respective roles in cell aggregation and β-lactam resistance. Together, these findings identify glucose oxidation-driven acidification as a metabolic trigger of envelope instability and OMV biogenesis in A. baumannii , linking glucose metabolism to envelope remodeling.