Discovery of the mechanism of adhesion to human cells of Mycoplasma genitalium

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Discovery of the mechanism of adhesion to human cells of Mycoplasma genitalium





Discovery of the mechanism of adhesion to human cells of Mycoplasma genitalium


Researchers from the Institute of Molecular Biology of Barcelona (IBMB-CSIC) and the Institute of Biotechnology and Biomedicine (IBB-UAB) (Catalunya, Spain) have discovered the mechanism by which the bacterium Mycoplasma genitalium (Mge) adheres to human cells . This adherence is essential for the establishment of the infection and the subsequent development of the disease.



The work, published in the journal Nature Communications, has been led by Ignacio Fita, a research professor at the Structural Biology Unit of IBMB-CSIC, and Óscar Quijada and Jaume Piñol, from the Molecular Biology laboratory at IBB-UAB. The first author of the work is David Aparicio, a postdoctoral researcher at IBMB-CSIC.



Mge is an emerging pathogen responsible for several genitourinary infections. In men, it is one of the main causes of urethritis (15-20%) and in women, it has been associated with cervicitis, pelvic inflammatory disease (PID), premature birth and spontaneous abortion.



Until now it was known that the adhesion of the bacterium to the genitourinary tract takes place by means of proteins, called adhesins, which recognize specific receptors on the surface of cells. In the case of Mge, these cellular receptors are known generically as sialic acids. Other important pathogens such as the flu virus also use sialic acids as receptors to bind to cells.



In this study, researchers from IBMB-CSIC have determined the three-dimensional structure of Mge P110 adhesin bound to these cellular receptors.







Images of transmission electron microscopy, in which the bacterium Mycoplasma genitalium (Mge) attached to the surface of a human cell (upper images) and penetrating inside (lower images) is observed. The image has been edited to facilitate the identification of mycoplasma (colored in blue). (Photo: UAB)



"We have made crystals containing P110 adhesin bound to sialic acids and we have diffractioned them with X-rays, which has revealed the exact position of the atoms in the protein and we have been able to define the structure in three dimensions", explains David Aparicio, IBMB researcher. The analyzes have been carried out in the Xaloc light line of the ALBA Synchrotron of Cerdanyola del Vallés using X-ray crystallography.



In parallel, IBB-UAB scientists have conducted in vivo studies with human cells and have shown that mutations in specific sites of the P110 protein prevent the binding of Mge. These results have confirmed the information derived from the obtained three-dimensional structure.



The results allow us to understand the molecular bases of Mge binding with human cells. "On the one hand, we have obtained key information about the colonization process, that is, the contact of the pathogen with the host cells. On the other, this allows us to develop alternative drugs to antibiotics capable of blocking the adhesion of Mge to cells, as molecules that mimic cellular receptors, or that stimulate the formation of antibodies that inhibit the function of adhesins, "explains Óscar Quijada , researcher of the IBB.



The research has led to the application for an international patent and a collaboration has been initiated with the service and the microbiology research group of the Vall d'Hebron Campus with the aim of fighting against the emergence of resistance.



Currently, Mge infections are as common as gonorrhea, one of the most commonly known sexually transmitted infections. In addition, Mge is becoming a superbacteria resistant to all antibiotics currently available, a fact that will soon leave us without therapeutic alternatives. Understanding the mechanism that allows infection can help define new treatments to combat it.



Antibiotic resistance is an increasingly prevalent problem. Through genetic changes, many bacteria have developed the ability to resist antibiotics and continue to reproduce. Although it is a natural process, the misuse and abuse of these medications is accelerating the process.



Given that Mge is developing resistance to all available antibiotics, finding an alternative therapeutic strategy is especially relevant. The results obtained are essential for the design of new drugs, since they allow to define adhesion at the molecular level. (Source: UAB)

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