Structure of the Neisseria Adhesin Complex Protein (ACP) and its role as a novel lysozyme inhibitor

Pathogenic and commensal neisseria species produce an adhesin complex protein,which was first characterised in neisseria meningitidis (nm) as a novel surface-exposed adhesin with vaccine potential. in the current study,the crystal structure of a recombinant (r)nm-acp type i protein was determined to 1.4 å resolution: the fold resembles an eight-stranded β-barrel,stabilized by a disulphide bond between the first (cys38) and last (cys121) β-strands. there are few main-chain hydrogen bonds linking β4-β5 and β8-β1,so the structure divides into two four-stranded anti-parallel β-sheets (β1-β4 and β5-β8). the computed surface electrostatic charge distribution showed that the β1-β4 sheet face is predominantly basic,whereas the β5-β8 sheet is apolar,apart from the loop between β4 and β5. concentrations of rnm-acp and rneisseria gonorrhoeae-acp proteins ≥0.25 μg/ml significantly inhibited by ~80–100% (p<0.05) the in vitro activity of human lysozyme (hl) over 24 h. specificity was demonstrated by the ability of murine anti-neisseria acp sera to block acp inhibition and restore hl activity. acp expression conferred tolerance to hl activity,as demonstrated by significant 3–9 fold reductions (p<0.05) in the growth of meningococcal and gonococcal acp gene knock-out mutants in the presence of lysozyme. in addition,wild-type neisseria lactamica treated with purified acp-specific rabbit igg antibodies showed similar fold reductions in bacterial growth,compared with untreated bacteria (p<0.05). nm-acpi is structurally similar to the mlic/plic protein family of lysozyme inhibitors. however,neisseria acp proteins show <20% primary sequence similarity with these inhibitors and do not share any conserved mlic/plic sequence motifs associated with lysozyme recognition. these observations suggest that neisseria acp adopts a different mode of lysozyme inhibition and that the ability of acp to inhibit lysozyme activity could be important for host colonization by both pathogenic and commensal neisseria organisms. thus,acp represents a dual target for developing neisseria vaccines and drugs to inhibit host-pathogen interactions. © 2017 humbert et al.