A research group from the Institute of Biomedicine of Valencia (IBV), of the Higher Council for Scientific Research (CSIC), has carried out a study that provides new clues about the molecular bases of the communication system used by bacteriophages to deploy their strategy when infecting to bacteria. The results of the study, in which researchers from Imperial College London collaborate, open up the possibility that different species of phages can communicate with each other. Although the biological function of this communication is unknown, the finding could be used to activate these microorganisms against pathogenic or antibiotic-resistant bacteria.
Bacteriophages (also called phages) are the most abundant organisms on Earth. They are viruses that only infect bacteria with strategies that vary according to their life cycles: lysis or lysogeny. In the lytic cycle, after infecting the bacterium, they multiply, generating multiple copies that are released into the medium by destroying (lysing) the infected bacterium. In the lysogenic, they are integrated into the genome of the bacterium without damaging it, becoming part of it for generations. In this state they can receive an activating signal and go through the lytic cycle, generating new copies and lysing (destroying) the host cell, something similar to herpes or hepatitis delta viruses in humans.
Phages can choose between both strategies, although in most cases the reasons are unknown. Recently, a mechanism called arbitrium (decision, in Latin) was discovered, which is used by some phages to make this decision between lysis or lysogeny. “It is a simple and elegant system used by phages to communicate and assess the number of relatives in the environment in relation to the bacteria available to infect,” explains Alberto Marina, a researcher who directs the IBV’s Macromolecule Crystallography Unit. CSIC that has carried out the study.
Once the bacterium is infected, the phage produces a message (a small molecule called AimP), which it pours into the environment and is heard by the receptor produced by other phages in neighboring bacteria, deciding between one life cycle or another. “If neighboring bacteria are not infected, AimP levels will be low and the phage will lyse, producing more progeny and infecting available bacteria. On the contrary, if the surrounding bacteria are infected, the AimP levels will be high and the phage will remain in lysogeny, since, if it generates progeny, it would not find free bacteria to infect”, describes Francisca Gallego, research technician at the CSIC in the IBV and first signatory of the work.
Utility of interphage communication
According to the initial description of arbitrium, a phage would only communicate with its progeny, each phage using an AimP molecule with a different sequence. That is, each phage speaks only to its relatives. However, the IBV team, in collaboration with the group led by José R. Peneadés, from the Center for Molecular Biology and Infection (Imperial College, London), has characterized the arbitrium system of a new phage (Katmira, which infects the bacterium Bacillus subtilis) by X-ray diffraction, confirming the molecular mechanism of the decision between lysis and lysogeny in phages with an arbitrium system.
“The comparison of different systems has allowed us to understand how the AimP molecule is read, showing that the differentiation between messages is weak”, says Alberto Marina. According to the IBV researcher, this opens the door to cross-regulation between phages in the regulation of the lysis-lysogeny decision. “In addition to defining the molecular bases of the arbitrium system, with this work we show that it is possible for different phages to communicate with each other, which is called cross-talk, and that some can also control others (cross-regulation). This would mean a new advance in communication within the microbial world.”
High precision antibiotics
The biological function of this communication remains to be elucidated, that is, if the phages use it to cooperate, deceive (spreading fake news to the environment) or compete. In the field of study applications, Marina highlights that “the results obtained would allow the use of the arbitrium system within the field of phage therapy, which consists of using phages to fight against pathogenic or multi-resistant bacteria to antibiotics, respecting the bacteria commensal and beneficial. That is, to use them as very high-precision antibiotics.”
Source: CSIC
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