Jumbo phage chimallin (ChmA) protein: The answer to CRISPR-Cas bacterial defense system?

Chimallin covering phage genome
Loughlin et, 2020

Jumbo phages are bacteriophages (phages) with genetic information (genomes) larger than 200 kilobases. These phages are known as "jumbo" because they have a huge genome size. In addition, they exhibit several novel characteristics not seen in smaller genome phages, which distinguish jumbo phages in aspects of genome and virion structure, progeny propagation, and evolution. According to some studies, jumbo phages can be useful in various ways in this era of antibiotic resistance. They have proven to be more effective than other phages, particularly when dealing with bacterial defense systems and infectivity.


Bacteria encode a plethora of defenses against foreign nucleic acids, and mechanisms like restriction-modification and CRISPR-Cas systems that target invading bacteriophage genome sequences are also present. In rebuttal, some families of jumbo bacteriophages protect their replicating genomic information in a nucleus-like compartment while excluding host defense factors. However, the main structure and composition of this compartment are unknown. According to the University of California, San Diego researchers, a jumbo phage nuclear shell primarily comprises one protein, Chimallin (ChmA). This protein self-assembles as a flexible sheet into closed micrometer-scale compartments growing a shield around the genetic material.

The genomic content of these Jumbo phages is diverse enough to obstruct the detailed comparative analysis that can benefit the study, use, and manipulation of smaller phages of which their genomes are abundantly available in databases. Despite this, there is still a relationship between Jumbo and smaller phages in their genomic and physical structure, which provides a link between the two. Understanding the uniqueness that will be exploited by transferring the better-known genome organization's knowledge and evolutionary mechanisms which are seen in smaller phages to jumbo phages is critical. The Chimallin protein and many other characteristics can be implemented directly using jumbo phages for therapy and other applications or indirectly through recombination technology by enabling other smaller genome phages to have a “special-hybrid” ability. 

 References
  • Yuan Y, Gao M. Jumbo Bacteriophages: An Overview. Front Microbiol. 2017 Mar 14;8:403. DOI: 10.3389/fmicb.2017.00403. PMID: 28352259; PMCID: PMC5348500.
  • Laughlin, T.G., Deep, A., Prichard, A.M., et al. Architecture and self-assembly of the jumbo bacteriophage nuclear shell. Nature 608, 429–435 (2022). https://doi.org/10.1038/s41586-022-05013-4

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