Friday 23 July 2021

They discover how a protein of the immune system kills bacteria and fungi

 Lactoferrin is an innate immune system protein present in mucous fluids such as saliva and milk and which has recognized antimicrobial capacity since its discovery more than 30 years ago. The mode of action by which this protein causes the death of microorganisms has not, however, been disclosed until now. Researchers from the Department of Functional Biology of the University of Oviedo have discovered the mechanism of antimicrobial action of lactoferrin, in simple terms, they have described how this substance eliminates bacteria and fungi.

Scientists from the Asturian academic institution have shown that this protein specifically inhibits an enzyme essential for the survival of these microorganisms - bacteria and fungi - called H + -ATPase. By blocking their activity, microorganisms cannot generate energy (ATP) nor can they control their internal pH. Both the generation of ATP - energy to grow and multiply - and the control of intracellular pH are essential to maintain cell viability. If the H + -ATPase protein does not work, the cell depletes its energy reserves and dies. In addition, by not being able to control the pH, the interior of the cell becomes acidic and other enzymes also stop working.

The finding of the mechanism of antimicrobial action of lactoferrin has just been published in the international journal Antimicrobial Agents and Chemotherapy of the American Society for Microbiology. Professor José Fernando Fierro, principal investigator and professor at the Department of Functional Biology, explains that, despite being an eminently basic research, at least two applications can be extracted from the work.

On the one hand, a new pasteurization method emerges, not described so far, already protected by a Spanish patent, which aims to take advantage of the natural presence of lactoferrin in milk to achieve cold pasteurization , which, according to José Fernando Fierro , it will avoid the loss of some nutritional and organoleptic properties produced by hot pasteurization.

On the other hand, research has identified a therapeutic target on which new antimicrobial drugs can act. The professor at the University of Oviedo explains that the progressive resistance to antibiotics has promoted an intense search for new bacterial targets and for new alternative drugs to existing ones. "The search for bacterial and fungal + -ATPase inhibitors is one of the most current lines of research. An example of this is the discovery of diarylquinolines, which are already being used to treat tuberculosis resistant to the usual drugs," he says. .

The work of Asturian researchers provides, in addition to these potential applications, a new model for the study of programmed cell death, scientifically known as apoptosis. María Teresa Andrés, co-director of the study, indicates that yeasts are used in laboratories as apoptosis models. For this and until now, scientists have to induce uncontrolled (or uncontrolled) programmed cell death (or cell apoptosis). Lactoferrin induces this apoptosis by interacting exogenously and specifically with H +-Yeast ATPase, which facilitates the study of the chain of intracellular events that lead to cell death. Knowledge of the cellular physiology of apoptosis would allow its manipulation, by inducing or stopping apoptosis in tissues, with a therapeutic purpose.

The studies developed by the University of Oviedo will continue in collaboration with a group from Harvard Medical School (Boston, USA), which has accepted Dr. Maikel Acosta as a postdoctoral researcher, who is waiting to obtain a research grant to join to that group.

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