Researchers from Institute of Molecular Biology of Barcelona (IBMB-CSIC) –based in the Barcelona Science Park– and the Institute for Natural Science and Technology at the University of Osaka, has succeeded in determining the three-dimensional structure of proteins by means of which the bacteria Mycoplasma pneumoniae –that cause 40% of atypical pneumonias– attaches itself to human cells and initiates infection. From the structure, this team of scientists have designed antibodies that decrease this adhesion capacity and opens the door to develop new therapies and vaccines against this pathogen.

Mycoplasma pneumoniae is a human pathogen that causes up to 40% of atypical primary pneumonias, a type of respiratory infections that can lead to serious complications. In fact, it is estimated that in 25% of cases, symptoms can spread out of the lungs and cause neurological, hepatic or cardiac effects.

Now, a team of researchers led by David Aparicio, from Institute of Molecular Biology of Barcelona (IBMB-CSIC), and Makoto Miyata, from the Institute for Natural Science and Technology at the University of Osaka, have discovered the mechanism by which the bacteria that cause 40% of atypical pneumonias adhere to the lungs, which has allowed them to design antibodies that decrease this adhesion capacity and opens the door to develop new therapies and vaccines against this pathogen.

The work, whose first author is David Vizarraga, predoctoral researcher at the IBMB-CSIC, will allow develop new therapeutic strategies based on adhesion blocking, a mechanism that was already known, but the structure of the proteins involved in this process had never been determined.

A mechanism based on an adhesion complex

Mycoplasma pneumoniae is a human pathogen that causes up to 40% of atypical primary pneumonias, a type of respiratory infections that can lead to serious complications. In fact, it is estimated that in 25% of cases, symptoms can spread out of the lungs and cause neurological, hepatic or cardiac effects.

It was known, for example, that the bacterium adheres to cell receptors that are generically known by the name of sialic acids, receptors that are used by other important pathogens to bind to cells, such as the bacterium Mycoplasma genitalium or the influenza virus.

At the Institute of Molecular Biology of Barcelona of the CSIC they have obtained crystals that contained the proteins P1 and P40 / P90 bound to sialic acids and have analyzed them with X-rays, in the Xaloc line of the ALBA Syncroton, which has allowed visualize the three-dimensional structure of these proteins.

“We have seen that the binding site for sialic acids is in P40 / P90 and not in the P1 protein, as previously thought, and we have identified two well-differentiated parts in the P1 protein, one with a high genetic variability and clinical (in the N-terminal region) and another much more conserved (in the C-terminal end) “, has detailed Aparicio.

“This information has helped us design antibodies that bind to the most conserved part of the protein in order to block the adhesion of the bacteria to human cells “, added Vizarraga.

According to the researcher at the Hospital Parc Taulí, Óscar Quijada, “trials with patients infected by Mycoplasma pneumoniae reveal that the C-terminal end of the P1 protein generates a strong immune response and in the long term, characteristics that make it an ideal candidate for vaccine development.”

► Reference article: Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Vizarraga et al.Nature Communications, https://doi.org/10.1038/s41467-020-18777-y

► More information: IBMB-CSIC website [+]