Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

Acinetobacter baumanniiis a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence inA.baumanniiremain uncertain. By comparing genomes among a panel ofA.baumanniistrains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact genegtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenicgtr6mutants, we confirmed thatgtr6-disrupted strains were protected from phagocytosisin vitroand displayed higher bacterial burden and lethalityin vivo.Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illnessin vivo. We found that the CR3 receptor mediated phagocytosis ofgtr6+, but notgtr6-, strains in a complement-dependent manner. Furthermore, hypovirulentgtr6+strains demonstrated increased virulencein vivowhen CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multipleA.baumanniistrains. Thus, capsular structure can determine virulence amongA.baumanniistrains by altering bacterial interactions with host complement-mediated opsonophagocytosis.