Planktonic Aggregation Enhances Antibiotic Tolerance in Non-MDR Acinetobacter baumannii

<i>Acinetobacter baumannii</i> relies on biofilms for antibiotic resistance, but the role of planktonic aggregates in drug tolerance is uncharacterized. We studied 103 clinical isolates to explore how the RND efflux pump gene <i>adeG</i> regulates aggregation. Non-MDR strains (with RND deletions) formed aggregates more frequently (13.79%, 4/29) than MDR strains (1.35%, 1/74), driven by residual RND efflux activity (not just deletions). <i>adeG</i> deletion induced 1-2 mm aggregates in a strain with combined <i>adeR</i>/Δ<i>adeABC</i> defects (via upregulated adhesion genes/hydrophobicity) but not in one with only Δ<i>adeC</i>. Aggregates boosted antibiotic tolerance (2-4-fold higher survival vs. disaggregated/parental strains) via metabolic dormancy (5-fold lower ATP), maintained growth in human serum, and promoted persistent bacteremia in immunosuppressed mice. Proteinase K disrupted aggregates, confirming protein matrices' role. These findings identify planktonic aggregates as pivotal adaptive and virulence-related targets for combating refractory non-MDR <i>A. baumannii</i> infections while also revealing an association between <i>adeG</i>-related genetic contexts and aggregate formation in the bacterium.