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

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.This work was supported by grants BFU2018-101265-B-100 (MINECO) to I.F., BIO2017-84166-R (MINECO) to J.P., and BES-2015-076104 (MINECO) to M.L.S., JSPS KAKENHI Grant Number JP25000013 to K.N., and a FEDER project from Instituto de Salud Carlos III (ISCIII, Acción Estratégica en Salud 2016). This work has also been funded by the Platform Project for Supporting Drug Discovery and Life Science Research (BINDS) from AMED under Grant Number JP19am0101117 to K.N. (support number 1282), by the Cyclic Innovation for Clinical Empowerment (CiCLE) from AMED under Grant Number JP17pc0101020 to K.N., and by JEOL YOKOGUSHI Research Alliance Laboratories of Osaka University to K.N. This work was supported by a Grant-in-Aid for Scientific Research on the Innovative Area “Harmonized Supramolecular Motility Machinery and Its Diversity” (MEXT KAKENH, JP24117002 to M.M., JP25117530 and JP15H01337 to T.K.), Grants-in-Aid for Scientific Research (B) and (A) (MEXT KAKENHI, JP24390107, JP17H01544), JST CREST (JPMJCR19S5), Osaka City University (OCU) Strategic Research Grant 2018 for top priority researches to M.M. D.A. acknowledges a María de Maeztu Unit of Excellence grant MDM-2014-0435