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Non-antibiotic strategies against ‘Mgen’, an emergent and sexually transmitted pathogen

Researchers from the CSIC and the UAB have discovered the mechanism by which the bacterium Mycoplasma genitalium (Mgen) adheres to human cells. This pathogen is becoming resistant to current antibiotics. The discovery will enable the development of non-antibiotic strategies to stop the bacterial adhesion to cells and, therefore, the infection. The research has led to an international patent application.

Transmission electron microscopy images in which the bacterium Mycoplasma genitalium (Mgen) can be observed adhered to the surface of a human cell (top images) and penetrating the interior of the cells (bottom images). Imatges have been edited to facilitate the identification of the mycoplasma (in blue).The study, was led by Ignacio Fita, research lecturer of the Structural Biology Unit at the IBMB-CSIC, and Oscar Quijada and Jaume Piñol, researchers from the Molecular Biology Lab, IBB-UAB. The first author of the study is David Aparicio, postdoctoral researcher at the IBMB-CSIC. The results have been published in the journal Nature Communications. 

Mgen is an emerging pathogen responsible for several infectious genitourinary disorders. In men, it is the most common cause of urethritis (15-20%) while in women, it has been associated with cervicitis, pelvic inflammatory disease (PID), premature birth and spontaneous abortions.

So far, it was known that adherence to the genitourinary tract was possible thanks to proteins known as adhesins, which recognise specific cell surface receptors. In the case of Mgen, these cell receptors are generically known as sialic acids. Other important pathogens such as the influenza virus also use sialic acids to adhere to cells.

In this study, IBMB-CSIC researchers determined the three-dimensional structure of the Mgen's P110 adhesins interacting with these cell receptors.

The scientists obtained the structure of P110 adhesine, a protein of the bacteria, interacting with the cell receptors, and have found some mutations in P110 that avoid this adhesion

"We made a crystal structure of the P110 adhesin bound to sialic acids and used X-rays  to determine the exact position of the atoms within the protein, and we were able to define the structure three-dimensionally", explains IBMB researcher David Aparicio. The experiments were conducted at the ALBA Synchrotron located in Cerdanyola del Vallès using X-ray crystallography.

At the same time, IBB-UAB scientists conducted in vivo studies with human cells and demonstrated that mutations in specific sites of the P110 protein prevent the adherence of Mgen. These results were fundamental to confirm the information obtained from the three-dimensional structure.

The results allow a better understanding of the molecular bases of the Mgen interaction with human cells. "On the one hand, we have obtained key information on the process of colonisation, that is how the pathogen comes into contact with the host cells. On the other hand, it allows us to develop alternative drugs capable of blocking Mgen's cell adhesion, such as molecules mimicking the human cell receptors, or stimulating the formation of antibodies which can inhibit the function of these adhesins", explains IBB research Oscar Quijada.

The research has led to an international patent application and a new collaboration with the Microbiology Department and research group from the Vall d'Hebron Campus with the aim of fighting against the emergence of new resistances.

Currently, Mgen infections are as frequent as gonorrhoea infections, one of the most common sexually transmitted diseases. In addition, Mgen is becoming a superbug capable of resisting all available antibiotics.

Contact:

Isabel Masip
VATC-CSIC
Tel 93 442 65 76
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