DIATEREI

Infective endocarditis (IE) is an infection of the heart valves. It occurs when bacteria or fungus reach damaged or inflamed areas of the heart through the blood stream and adhere to them. If it is not treated quickly, the infection causes very serious injuries and complications to the valves, and has a mortality incidence around 30-40%. The treatments include antibiotics, anticoagulant prophylaxis and, in certain cases, heart valve replacement surgery, which in turn is associated with an increase in patient morbidity.

In this collaborative project we used endocarditis caused by Staphylococcus aureus (S. aureus), which is the most aggressive and frequent one in our environment, as a model to deepen our knowledge of two problems related with this pathology: the differences in prevalence and prognosis depending on gender and the difficulties of antibiotic treatment caused by multi-drug resistant bacteria. In the first goal, we identified the changes that occur in the endothelium cells and the interstices of heart valves when an infection occurs, combining molecular biology and single-cell transcriptomics techniques and determining potential differences depending on patient gender. That approach let us find potential new gender-specific therapeutic targets for patients, which will make it possible to personalise and individualise IE treatment. The second goal was to develop a treatment strategy complementary to antibiotics based on functionalized virus (phages) that contain the CRISPR-Cas9 system with gRNA directed towards conserved regions of the S. aureus chromosome. That approach is based on the phage inserting the CRISPR system into the bacteria that will be responsible for directing the bacterial chromosome causing the inactivation of the bacteria when it infects. Experiments were done at a cellular level and using an experimental IE model. In addition, it was possible to functionalise the phages with magnetic particles, which will make it easier to concentrate phages in the infection area.

This project made it possible to study the cellular and molecular mechanisms responsible for IE caused by S. aureus, as well as the possible differences in prevalence and prognosis for the disease between men and women. We intend to improve the options for personalising IE treatment with it. On the other hand, the data obtained thanks to the project has made it possible for us to propose a new therapeutic alternative based on phages functionalized with magnetic particles that destroy bacteria and stop infections.