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Bacteria’s self-destruct mechanism

In the battle that has lasted for over billion of years, both bacteria and bacteriophages have developed their own mechanisms against one another. CRISPR-Cas system is a well-known mechanism that is used by both bacteria and phages. Another immune mechanism that bacteria has evolved, is the CBASS or also referred to as the self-destruction mechanism.Researchers at the University of California School of Medicine in San Diego, have discovered an immune mechanism used by bacteria against phage infection. Such a mechanism functions like an abortive infection. In its essence, the bacterial cell decides to self-sacrifice itself in order to help save their colony. In such an act, it destroys the itself and ultimately brings the process that results in more bacteriophages, to an end. Such an act may seem illogical when viewed from a single celled organisms’ perspective, however, bacteria act as a cooperative community, which makes sense that one would sacrifice itself for the benefit of all within that community.

HORMA & CBASS system

In 2015, the National Institute of Bioinformatics of Health published that bacteria have the ability to produce the HORMA proteins. HORMA are specific protein which ensure the stability of cell genome during cell division. Professor Corbett (MD, Cell and Molecular Medicine in San Diego Schools), found the self-destruct mechanism in approximately 10 percent of 75,000 different bacterial genomes.It has also been proven that the HORMA protein has the capability to sense infection. This would deal for the synthesis of a second protein for the messenger molecule, which would activate the self-destruction mechanism by destroying the bacteria’s own genome and ultimately killing the cell. This would also ensure that the phage would be unable to replicate and terminate further infection of bacterial cells. After studying over 6,000 distinct CBASS systems, researchers found that each encodes a different set of signaling proteins, effector proteins and infection sensors. A deeper and holistic understanding of how all the different parts match up and work together will give more information on how the system can be used towards therapies.According to Dr. Corbett, researchers at the University of California at the San Diego’s Center for Innovative Phage Technology and Phage Therapy, could use the information on bacteria’s self-destruct mechanism, to create phage therapies impervious to CBASS, resulting in bacteriophage therapy more effective. Another approach would be to find a trigger of the CBASS system within the bacteria to be able to activate this mechanism, resulting in bacteria to kill itself.

Research sources:

Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity.

Rebecca K. Lau, Qiaozhen Ye, Stephen B. Erica A. Birkholz, Kyle R. Berg, Lucas Patel, Ian T. Mathews, Jeramie D. Watrous, Kaori Ego, Aaron T. Whiteley, Brianna Lowey, John J. Mekalanos, Philip J. Kranzusch, Mohit Jain, Joe Pogliano and Kevin D. Corbett. Published in Molecular Cell 2020 | DOI: 10.1016/j.molcel.2019.12.010

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