In Vivo Cross-Linking MS Reveals Conservation in OmpA Linkage to Different Classes of β‑Lactamase Enzymes

Molecular interactions between two different classes
of β-lactamase
enzymes and outer membrane protein A (OmpA) were studied by in vivo
chemical cross-linking of a multi-drug-resistant strain of Acinetobacter baumannii AB5075. Class A β-lactamase
blaGES-11 and Class D β-lactamase Oxa23, responsible for hydrolysis
of different types of β-lactam antibiotics, were found to be
cross-linked to similar lysine sites of the periplasmic domain of
outer membrane protein OmpA, despite low sequence homology between
the two enzymes. The findings from in vivo XL-MS suggest that the
interacting surfaces between both β-lactamase enzymes and OmpA
are conserved during molecular evolution, and the OmpA C-terminus
domain serves an important function of anchoring different types of
β-lactamase enzymes in the periplasmic space.