Bacterial resistance to antibiotics is one of the main global threats to public health. One of the strategies to combat these super resistant bacteria is based on the use of viruses, called bacteriophages, which are harmless to people.
The potential of these viruses has been known since the beginning of the last century, but current resistance to antibiotics makes them a priority research avenue. now the group UPOBioinfowho carry out their research in the Andalusian Center for Developmental Biology (CABD)described in an article published in the journal Science Advances a relationship between the proteins present in the membrane of bacteria and the CRISPR-Cas immunity systems of virus resistance.
The work was carried out in collaboration with the University of Mainz (Germany) and the infectious diseases group at the Institute of Biomedicine in Seville.
The CRISPR Cas systems, present in 40% of bacteria, allow them to be immune to bacteriophage viruses, thanks to the fact of recognizing them by their genome; These DNA fragments possessed by some bacteria were mostly unknown –the so-called ‘dark matter’–, that is, it was not known what protected them against, point out the authors.
Bioinformatics analysis performed by the CABD researchers showed that this CRISPR dark matter is used to recognize hitherto unknown bacteriophage viruses, reducing CRISPR dark matter from 80% to just 15% in some species.
A better understanding of the mechanisms by which bacteria defend themselves against viruses, and why some have ‘vaccines’ and others don’t, could be the key to advancing the strategy of using viruses to fight bacterial infections. For this reason, researchers from the UPOBioinfo group analyzed more than 68,000 genomes of superresistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa or Klebsiella pneumoniae and found a relationship between the outer membrane of bacteria and their ability to defend against viruses using CRISPR -Cas.
This new theory called the Membranoma-Page-CRISPR triad shows that there are bacteria with unique proteins on their surface that allow them to have greater advantages in their environment, including resistance to antibiotics, but can also be the gateway for specific viruses.
To compensate for this weakness, bacteria are equipped with CRISPR-Cas systems; All of this would explain why these bacterial vaccination systems are not universal. The UPOBioinfo team demonstrated this theory in CRISPR-Cas immunization systems in four of the six bacteria studied.
In this way, the discovery represents a breakthrough for a crucial question in the evolution of bacteria and useful in phage therapy: why do some bacteria have systems for vaccinating against viruses and others do not? But, above all, knowing the details of the war between bacteria and bacteriophage viruses will make it possible to fight infections caused by super-resistant bacteria more efficiently in the future, the researchers conclude.
Reference: Rubio, A. et al. ‘Analysis of bacterial pangenomes reduces CRISPR dark matter and reveals strong association between membrane and CRISPR-Cas systems’. ‘Science advances’ (2023)