Monoclonal Antibody Targeting The Ss-Barrel Assembly Machine Of Escherichia Coli Is Bactericidal

The folding and insertion of integral ss-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect ss-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize amonoclonal antibody that selectively inhibits an essential component of the Escherichia coli ss-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E. coli strain with truncated LPS. Direct binding of MAB1 to an extracellular BamA epitope inhibits its ss-barrel folding activity, induces periplasmic stress, disrupts outer membrane integrity, and kills bacteria. Notably, resistance to MAB1-mediated killing reveals a link between outermembrane fluidity and protein folding by BamA in vivo, underscoring the utility of this antibody for studying ss-barrel membrane protein folding within a living cell. Identification of this BamA antagonist highlights the potential for new mechanisms of antibiotics to inhibit Gram-negative bacterial growth by targeting extracellular epitopes.