Histones against bacterial infections
A study involving UAB researchers has analysed the antimicrobial activity of human histones against different bacteria, both in solution and in biofilm. The results open the door to finding new, more effective treatments, particularly against Pseudomonas aeruginosa infections. This bacterium is mainly responsible for the development of chronic wounds and lung failure in patients with cystic fibrosis and other respiratory diseases.
The study was carried out with the participation of Inmaculada Ponte and Alícia Roque, researchers from the Department of Biochemistry and Molecular Biology at the UAB. Published in the American Society for Microbiology journal mSystems, it was led by Eduard Torrents, researcher at the Institute for Bioengineering of Catalonia (IBEC) and lecturer at the University of Barcelona (UB). CSIC researcher Albert Jordan also participated in the study.
The researchers provide results that could help develop more effective treatments to combat bacterial resistance. They described that human histones have antimicrobial activity against different bacteria, including biofilms of Pseudomonas aeruginosa, one of the six most resistant bacteria in the world.
Histones are key proteins in the organisation and regulation of DNA in all eukaryotic cells, i.e. cells in which DNA is contained in a nucleus. This includes fungi, plants and animals. However, in addition to this function, it has been shown that in certain situations histones of subtype H1 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 surrounding the microorganisms, causing damage that ultimately leads to their death.
The researchers analysed the antimicrobial activity of three subtypes of human histone H1 against different bacteria, and specifically observed a reduction of up to 70% in the number of bacteria after treatment in P. aeruginosa. Furthermore, the combination of histones with the antibiotic ciprofloxacin had a greater effect than when each was administered separately, opening the door to the development of more effective treatment cocktails.
The research team also studied histone activity against P. aeruginosa biofilms and found a 30% reduction in bacterial mass. Biofilms are communities of microorganisms, including bacteria, fungi and viruses, that adhere to living or inert surfaces, such as tissues, organs or medical devices. Their peculiarity lies in the secretion of an extracellular matrix that encapsulates and protects the microorganisms, hindering the action of the immune system and antibiotics, making them particularly difficult to treat.
These findings suggest that the use of histones or parts of these proteins, either alone or in combination with antibiotics or other molecules with antimicrobial activity, is a promising alternative to combat acute and chronic infections caused by pathogens such as P. aeruginosa and other multidrug-resistant bacteria.
The results were confirmed in in vivo tests on wax worms (Galleria mellonella) infected with P. aeruginosa. Infected larvae treated with the histones showed an increase in survival time compared to untreated larvae. Furthermore, the treatment did not cause any toxic or adverse effects.
The results obtained are particularly relevant because biofilms are highly resistant to antibiotics and cause severe infections. The next steps include determining the molecular part of the histone with the most antimicrobial capacity and validating the use of histones in the clinic.
Referenced article: Arévalo-Jaimes BV, Salinas-Pena M, Ponte I, Jordan A, Roque A, Torrents E. Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections. mSystems (2024). https://doi.org/10.1128/msystems.00704-24