Microbiologists have studied bacterial protection mechanisms in opposition to phages for many years. However till lower than a decade in the past, there have been only some recognized bacterial immune techniques: induced suicide mechanisms, restriction-modification, and CRISPR-Cas techniques.1-3
In 2018, microbiologist Rotem Sorek and his colleagues on the Weizmann Institute revealed that bacterial antiphage protection mechanisms are rather more numerous than initially thought.4 Since then, Sorek’s crew and others have found quite a few novel bacterial immune techniques, together with the Bil system (a major part of the system is the Bil protein).5 Sorek subsequent needed to grasp how the Bil system works.
Damaging staining transmission electron microscope picture of tailless phages from lysates of Bil-expressing micro organism.
Jens Hör
In a current examine in Nature, Sorek and his colleagues confirmed that micro organism can use this method to covalently connect the bacterial protein Bil to the spike protein of an infecting phage’s tail, which is essential for the tail meeting of its progenies and the an infection of recent host cells.6 The researchers famous that the presence of Bil in phage-infected micro organism resulted within the manufacturing of phage progenies that have been both tailless or absolutely assembled however much less infectious, defending the remainder of the bacterial inhabitants.
The Bil system is mechanistically just like ubiquitin pathways as a result of it includes the covalent attachment of ubiquitin-like proteins (Ubl) by ubiquitin-conjugating enzymes.7 Sorek’s curiosity within the Bil protein first piqued due to its structural similarity to interferon-stimulated gene 15 (ISG15), a human Ubl, which is the way it acquired its identify (bacterial ISG15-like, or Bil for brief).8 In people, ISG15 is a part of an innate antiviral protection pathway that’s recognized to guard in opposition to HIV and influenza, though its mechanism is just not well-understood.
“Many of those bacterial techniques have been proven to be the evolutionary origin of various human immune techniques,” stated microbiologist Jens Hör, a former postdoctoral fellow in Sorek’s lab and coauthor of the examine. “We thought that if we determine the way it works in micro organism, we’d additionally advance the human area a bit.”
Jens Hör is a microbiologist on the Helmholtz Institute. Hör was a postdoctoral fellow in Rotem Sorek’s laboratory on the Weizmann Institute and coauthor of the examine.
Jens Hör
Kevin Corbett, a structural biologist on the College of California, San Diego who was not concerned within the examine, stated that Bil appears to actually resemble the eukaryotic ubiquitination equipment. Corbett and his group concurrently revealed a paper on the structural and molecular particulars of the Bil system in the identical problem of Nature.9
“That is the primary time that micro organism have been proven to carry out protein conjugation utilizing equipment like this, notably a ubiquitin-like protein,” stated Corbett.
Kevin Corbett, structural biologist on the College of California, San Diego. Corbett’s group concurrently revealed a paper that centered on the structural and molecular particulars of Bil in Nature.
Kevin Corbett
To know how Bil works, Sorek’s crew in contrast phage progeny from contaminated micro organism with and with out the system. They carried out density gradient centrifugation to separate phages from bacterial lysates and located that the micro organism that expressed Bil produced a better density band within the gradient. When the scientists remoted the upper density band and considered it beneath a transmission electron microscope, they have been shocked by the sight of tailless phages. The crew believes that the upper buoyant density could possibly be defined by the upper DNA-to-protein ratio in tailless phages.
Whereas not all of the phage progenies find yourself tailless, Sorek and his crew confirmed that even the absolutely assembled progenies confirmed a decreased functionality of infecting different cells. By performing immunoprecipitation mass spectrometry, the authors confirmed that Bil is particularly conjugated to the spike protein on the tip of the phage’s tail. Hör stated that Bil’s conjugation to the spike protein probably inhibits the interplay between the phage and its entry receptor on new host cells, which may clarify why among the tailed progenies are unable to contaminate.
Hör talked about that some phages have enzymatic domains of their tails that would reverse Ubl conjugation reactions just like the one carried out by Bil. “One essential query that we didn’t reply in our examine is how phages can overcome bacterial protection by the Bil system,” he stated.
- Lopatina A, et al. Abortive an infection: Bacterial suicide as an antiviral immune technique. Annu Rev Virol. 2020;7(1):371-384.
- Heitman J. On the origins, constructions and features of restriction-modification enzymes. Genet Eng (N Y). 1993;15:57-108.
- Hille F, Charpentier E. CRISPR-Cas: Biology, mechanisms and relevance. Philos Trans R Soc Lond B Biol Sci. 2016;371(1707):20150496.
- Doron S, et al. Systematic discovery of antiphage protection techniques within the microbial pangenome. Science. 2018;359(6379):eaar4120.
- Millman A, et al. An expanded arsenal of immune techniques that shield micro organism from phages. Cell Host Microbe. 2022;30(11):1556-1569.e5.
- Hör J, et al. Micro organism conjugate ubiquitin-like proteins to intrude with phage meeting. Nature. 2024;631(8022):850-856.
- Cappadocia L, Lima CD. Ubiquitin-like protein conjugation: Buildings, chemistry, and mechanism. Chem Rev. 2018;118(3):889-918.
- Perng YC, Lenschow DJ. ISG15 in antiviral immunity and past. Nat Rev Microbiol. 2018;16(7):423-439.
- Chambers LR, et al. A eukaryotic-like ubiquitination system in bacterial antiviral defence. Nature. 2024;631(8022):843-849.
