Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae
David Vizarraga, Akihiro Kawamoto, U. Matsumoto, R. Illanes, R. Pérez-Luque, Jesús Martín, Rocco Mazzolini, Paula Bierge, Òscar Q. Pich, Mateu Espasa, Isabel Sanfeliú, Juliana Esperalba, Miguel Fernández-Huerta, Margot P. Scheffer, Jaume Pinyol, Achilleas S. Frangakis, María Lluch‐Senar, Shigetarou Mori, Keigo Shibayama, Tsuyoshi Kenri, Takayuki Kato, Keiichi Namba, Ignacio Fita, Makoto Miyata, David Aparicio
Abstract
Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae, and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections.