Histones to stop bacterial infections

Antibiotics have saved millions of lives from infectious diseases, being considered one of the most relevant discoveries of the 20th century. However, the increasing use (and abuse) of antibiotics over all these years has led many bacteria to develop resistance to these drugs.

Bacterial resistance to antibiotics is a global crisis that makes it difficult to treat common infections, and is estimated to be the cause of at least 1.27 million deaths worldwide. Pathogens such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa have developed resistance to multiple antibiotics, increasing mortality rates, prolonging hospital stays and raising healthcare costs. Without new antimicrobial strategies, it is estimated that by 2050 resistant infections could cause 10 million deaths annually worldwide.

In a recent study, a team made up of, among others, Betsy Verónica Arévalo-Jaimes and Eduard Torrents, both from the Institute of Bioengineering of Catalonia (IBEC), have obtained results that can help in the development of more effective treatments to combat resistance bacterial. The authors of the study have described that human histones have antimicrobial activity against different bacteria, including biofilms of Pseudomonas aeruginosa, one of the 6 most resistant bacteria in the world.

This work has been developed in collaboration with Alicia Roque and Inmaculada Ponte, from the Autonomous University of Barcelona (UAB), as well as with Albert Jordan from the Higher Council for Scientific Research (CSIC), in Spain.

Histones are fundamental proteins in the organization and regulation of DNA in all eukaryotic cells, that is, in which the DNA is found within a nucleus. This includes, among others, fungi, plants and animals. However, in addition to this function, it has been seen in certain situations that histones of the H1 subtype can be released outside the cell and exert antimicrobial activity against bacteria, fungi, parasites and viruses. This activity is mainly attributed to the binding of histones to the membranes that surround the microorganisms, causing damage that ultimately leads to their death.

Betsy Verónica Arévalo Jaimes (left) and Eduard Torrents, in an IBEC laboratory. (Photo: IBEC)

Researchers have analyzed the antimicrobial activity of 3 subtypes of human histone H1 against different bacteria, specifically observing in P. aeruginosa a reduction of up to 70% in the number of bacteria after treatment. Furthermore, by combining histones with the antibiotic ciprofloxacin, the effect was greater than when each was administered separately, which opens the door to developing more effective treatment cocktails.

The research team has also studied the activity of histones against P. aeruginosa biofilms, finding a 30% reduction in bacterial mass. Biofilms, or biofilms, are communities of microorganisms that can include bacteria, fungi and viruses, attached to living or inert surfaces, such as tissues or organs, or medical devices. Its particularity lies in the secretion of an extracellular matrix that encapsulates and protects microorganisms, like a bunker, hindering the action of the immune system and antibiotics, which makes them especially difficult to treat.

The results have been corroborated in in vivo tests in wax worms (Galleria mellonella) infected with P. aeruginosa. Infected larvae treated with histones showed an increase in survival time compared to those that did not receive treatment. Furthermore, the treatment did not cause any toxic or negative effects.

The results obtained are especially relevant, since biofilms have a high resistance to antibiotics and cause very serious infections. It is crucial to identify new substances with antimicrobial activity, as well as new mechanisms of action against biofilms to develop more effective therapeutic strategies.

The study is titled “Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections.” And it has been published in the academic journal mSystems, from the American Society for Microbiology (ASM).

The next steps in this line of research and development include determining the molecular part of the histone that has the most antimicrobial capacity and validating the use of histones in clinical practice. (Source: IBEC)