Antibodies halting motility inMycoplasma pneumoniaereveal the dynamic nature of the adhesion complex

Abstract Mycoplasma pneumoniae is a bacterial wall-less human pathogen and the etiological agent of atypical pneumonia and tracheobronchitis in both adults and children. M. pneumoniae infectivity, gliding motility and adherence to host target respiratory epithelial cells, are mediated by adhesin proteins P1 and P40/P90 forming a trans-membrane complex that binds to sialylated oligosaccharides cell receptors. Here we report the Cryo-EM structure from P1 bound to the Fab fragment of monoclonal antibody (P1/MCA4), which stops gliding and induces detachment of motile M. pneumoniae cells. On the contrary, polyclonal antibodies generated against the N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. The epitope of P1MCA4, centred on loop Thr1426-Asp1438 in the small C-terminal domain of P1, is inaccessible to antibodies in the “open” conformation of the adhesion complex, when ready for attachment to sialylated oligosaccharides. Mutations in the highly conserved Engelman motifs found in the transmembrane helix of P40/P90, also alter adhesion and motility. The C-terminal domain of P1 experiences large conformational rearrangements, during the attachment/detachment cycle of the adhesion complex. These rearrangements are hindered by antibodies against the C-terminal domain interfering with gliding, which explains the specific neutralization mechanism deployed by antibodies against this domain and suggests new ways to confront M. pneumoniae infections.