Journal Article

Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae

Pich, Oscar Q., Fernández-Huerta, Miguel, Lluch-Senar, Maria, Fita, Ignacio, Sanfeliu, Isabel, Miyata, Makoto, Frangakis, Achilleas S., Namba, Keiichi, Matsumoto, U., Pérez-Luque, Rosa, Mori, Shigetarou, Aparicio, David, Esperalba, Juliana, Pinyol, Jaume, Mazzolini, Rocco, Martín, Jesús, Bierge, Paula, Illanes, Ramiro, Espasa, Mateu, Shibayama, Keigo, Kawamoto, Akihiro, Vizarraga, David, Scheffer, Margot P., Kenri, Tsuyoshi, Kato, Takayuki

2020

Overview

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. Adhesion of the human pathogen Mycoplasma pneumoniae to pulmonary epithelial cells is mediated by a transmembrane complex composed of proteins P1 and P40/P90. Here, the authors present the structures of M. pneumoniae P1 and P40/P90, show that P40/P90 binds sialylated oligosaccharides and have also determined the crystal structures of P40/P90 complexes with 3’-Sialyllactose and 6’-Sialyllactose, which provide insights into the mechanisms of adhesion and gliding on host cell surfaces.

• Publisher: Nature Publishing Group UK,Nature Portfolio
• Subject: 13/1 / 14/28 / 38/22 / 38/77 / 631/250 / 631/326 / 631/535 / 631/535/1258 / 631/535/1266 / Humanities and Social Sciences / multidisciplinary / Science / Science (multidisciplinary)