Researchers at the Faculty of Medicine of the Autonomous University of Madrid (UAM) have revealed that pipolins, mobile genetic elements present in bacteria, contain numerous defense systems against bacteriophages. The study, published in Nucleic Acids Research, analyzed more than 11,000 pipolins in bacterial genomes, identifying their crucial role in the genetic evolution of bacteria. The results could affect the development of new bacteriophage-based antimicrobial therapies.
Bacteria have evolved complex defense systems to survive in adverse environments, where one of the main threats are bacteriophages, viruses that infect and destroy bacteria. Mobile Genetic Elements (MGEs) are DNA fragments that move within or between genomes, playing a key role in the transfer of defense systems between bacteria. In addition, these elements allow the propagation of key genes for survival, such as those related to antibiotic resistance, heavy metals or virulence factors.
Among the diversity of MGEs, the group from the Faculty of Medicine of the Autonomous University of Madrid (UAM) led by Modesto Redrejo Rodríguez discovered in 2017 the "pipolins". These differ from other mobile genetic elements by encoding a DNA polymerase, called piPolB, which allows DNA replication without the need for an initiator RNA or a terminal protein.
In previous studies, the group had shown that pipolins have highly variable gene content, mainly related to DNA mobilization and metabolism. But surprisingly, they found no antibiotic resistance genes or virulence factors associated with these structures, leaving their biological role uncertain, as it was not known what selective advantage they could bring to their host.
Now, in recent research led by Víctor Mateo Cáceres, predoctoral researcher of the FPI-UAM program, more than 1.1 million bacterial genomes were analyzed and more than 11,000 pipolins were identified, finding them for the first time in well-known pathogenic species such as Salmonella enterica, Vibrio cholerae and Staphylococcus aureus.
Defense mechanisms in pipolins
Analysis of the genes encoded in these MGEs revealed to the researchers that pipolins contain, on average, more defense genes against bacteriophages than other MGEs, such as plasmids, conjugative integrative elements or satellite viruses.
Among the defense mechanisms present in pipolins, restriction-modification systems and helicases stand out, but researchers have also found a wide variety of systems characterized in recent years.
"In contrast, we observed a relative absence of antibiotic resistance genes, virulence factors or other genes that provide different adaptive advantages. This is surprising since MGEs do not a priori have to specialize in carrying a certain type of advantageous genes. In any case, this observation suggests that a possible biological role of pipolins is to participate in bacterial protection against viruses or other MGEs that try to enter the bacterium," says Redrejo Rodriguez.
The study, published in Nucleic Acids Research, also revealed that many defense systems contained in pipolins, especially in enterobacteria, have recently been exchanged with plasmids and other conjugative elements. "This suggests that pipolins do not act in isolation, but actively participate in the global network of MGEs that manages the repertoire of defense systems and facilitates their transfer to other bacteria," adds Mateo Cáceres.
In sum, the study assigns a biological role to this family of MGEs, which until now lacked a clear function. "The ability to exchange defense systems with other genetic elements reinforces the importance of pipolins in gene transfer mechanisms, allowing bacteria to adapt rapidly. This knowledge is key to understanding bacterial evolution and could have future implications in the development of new antimicrobial therapies based on bacteriophages," concludes Redrejo Rodríguez.
Bibliographic reference:
Víctor Mateo-Cáceres, Modesto Redrejo-Rodríguez. "Pipolins are bimodular platforms that maintain a reservoir of defense systems exchangeable with various bacterial genetic mobile elements", Nucleic Acids Research, 2024; gkae891, DOI: https://doi.org/10.1093/nar/gkae891
This research has been funded by the FPI-UAM program of the Universidad Autónoma de Madrid (SFPI/2023-00603); the Comunidad de Madrid (Ayudas para Jóvenes Doctores, V Plan PRICIT): SI3/PJI/2021-00271, and a Knowledge Generation project funded by MCIN/AEI/10.13039/501100011033 and "FEDER Una manera de hacer Europa" (PID2021-123403NB-I00).
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