Shaheera Rahman
Junior
School of Life Sciences
Independent University, Bangladesh
March 23rd, 2019
Viruses are the ultimate survivors. They have existed since the dawn of life on earth (if not before), and no matter what evolution has thrown at them, these obligate parasites have collectively continued to survive against seemingly much stronger hosts. Recent research on bacteriophages – viruses that infect bacteria – illuminates the variety of ways in which viruses interact with and exploit their environment.
Much is made of the battle for supremacy between bacteria and phages. But bacteria are not the only enemies that phages have to encounter; they also have to deal with other phages. A recent study on bacteriophages that infect Mycobacterium smegmatis showed that certain phages do not take kindly to the idea of sharing their host and like to keep their host to themselves [1]. They prevent other phages, both of the same and different types, from infecting the same host by various means. They can block the entrance of other phages, or bring the growth of the bacterial cell to a halt, which would also put a stop to the replication of lytic phages. Lytic phages rapidly replicate and ultimately lyse the host cell to leave; lysogenic phages, which incorporate themselves into the host genome, would clearly benefit from not having their long-term home (the host) destroyed! To regulate the bacterial cell growth, one of the phages studied appears to encode its own ppGpp synthetase. This enzyme synthesizes the molecule ppGpp, an alarmone which is normally involved in the transition of bacteria into the non-growing stationary phase when they run out of nutrients. The phage, therefore, deceives the bacterial cell into not growing. Unsurprisingly, another phage the authors looked at encodes a protein that inhibits ppGpp synthesis, which acts as an effective counter defense.
Junior
School of Life Sciences
Independent University, Bangladesh
March 23rd, 2019
Viruses are the ultimate survivors. They have existed since the dawn of life on earth (if not before), and no matter what evolution has thrown at them, these obligate parasites have collectively continued to survive against seemingly much stronger hosts. Recent research on bacteriophages – viruses that infect bacteria – illuminates the variety of ways in which viruses interact with and exploit their environment.
Much is made of the battle for supremacy between bacteria and phages. But bacteria are not the only enemies that phages have to encounter; they also have to deal with other phages. A recent study on bacteriophages that infect Mycobacterium smegmatis showed that certain phages do not take kindly to the idea of sharing their host and like to keep their host to themselves [1]. They prevent other phages, both of the same and different types, from infecting the same host by various means. They can block the entrance of other phages, or bring the growth of the bacterial cell to a halt, which would also put a stop to the replication of lytic phages. Lytic phages rapidly replicate and ultimately lyse the host cell to leave; lysogenic phages, which incorporate themselves into the host genome, would clearly benefit from not having their long-term home (the host) destroyed! To regulate the bacterial cell growth, one of the phages studied appears to encode its own ppGpp synthetase. This enzyme synthesizes the molecule ppGpp, an alarmone which is normally involved in the transition of bacteria into the non-growing stationary phase when they run out of nutrients. The phage, therefore, deceives the bacterial cell into not growing. Unsurprisingly, another phage the authors looked at encodes a protein that inhibits ppGpp synthesis, which acts as an effective counter defense.
Electron micrographs of some mycobacteriophages from Dedrick et al.
But bacteriophages do not always fight among themselves. In the face of adversity, certain phages stop fighting among themselves and come together to defeat the greater evil, that is, the bacterial defense system. Bacteria naturally do not like being preyed upon, and have evolved numerous defenses to counter the threat posed by phages. Among them, CRISPR (clustered regularly interspersed short palindromic repeats) provides a strikingly effective example.
In many bacteria, CRISPR-based systems allow bacterial cells to recognize and target foreign DNA. If the bacteria survive the first infection, they retain a piece of the viral DNA which serves as memory when the same virus attempts to infect the bacteria again. The response in the second instance is much faster and potent as the retained viral DNA encodes an RNA molecule that directs a caspase to cut the DNA of the infecting virus. This is how bacterial CRISPR/Cas immunity works. This is a very effective form of immunity and poses a great threat to the phages. However, phages have evolved to find ways to circumvent this system. Some phages encode anti-CRISPR (Acr) proteins that antagonize bacterial CRISPR-Cas immunity by binding components of its machinery. Another recent study, conducted on Pseudomonas aeruginosa and its phages, demonstrated that bacteria with CRISPR-Cas remain partially immune to Acr-encoding phages during single-phage infections [2]. In order to survive, the phages must cooperate.
The first infecting batch of the Acr-encoding phage blocks the CRISPR-Cas system, allowing subsequent infecting batches to replicate efficiently. The initial density of Acr-encoding phages that infect bacteria determines whether the phage population will go extinct or amplify.
Other bacteriophages deal with bacterial weaponry as lone wolves. In order to be self-sufficient, certain phages that infect Vibrio cholerae have now evolved to have mechanisms that can single-handedly defeat bacterial defenses. This was first demonstrated in a study published in 2013 [3]. Vibrio cholerae contain phage inducible chromosomal islands (PICI) which identify phage sequences and prevent the phages from replicating. However, some phages have managed to acquire from previous bacterial PICI-like elements in bacteria, rendering this defense useless. Demonstrating a vicious knack for manipulating aspects of their ecological environment to their advantage, these phages have acquired and coopted one of the defense systems that had evolved to kill them.
The vicissitudes of their existence as obligate parasites drive bacteriophages (and all viruses) to endlessly creative strategies to ensure their survival. We can marvel at their prowess, but perhaps we could also learn a lesson or two from these bacteriophages, as we wage an increasingly hopeless war against multidrug bacterial pathogens.
Bibliography:
1. Dedrick RM, Jacobs-Sera D, Bustamante CAG, et al.
Prophage-mediated defence against viral attack and viral counter-defence. Nat
Microbiol. 2017;2(3):16251. doi:10.1038/nmicrobiol.2016.251
2. Landsberger M, Gandon S, Meaden S, et al. Anti-CRISPR
Phages Cooperate to Overcome CRISPR-Cas Immunity. Cell.
2018;174(4):908-916.e12. doi:10.1016/j.cell.2018.05.058
3. Seed KD, Lazinski DW, Calderwood SB, Camilli A. A
bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate
immunity. Nature. 2013;494(7438):489-491. doi:10.1038/nature11927
Shaheera plans to go into biomedical research to figure out all the cures. Her hobbies include reading and eating.
