Monday Micro – smart viruses

By Siouxsie Wiles 04/03/2013

I’ve always loved bacteriophage, the spaceship-like viruses which prey on bacteria*. They really do look like something from another planet.

Phage are abundant in nature, found everywhere, from soil and water, to the guts of animals. They have two different life cycles; in the lytic cycle they infect bacteria, replicate themselves and then lyse and kill the bacteria as they spill out looking for more victims to infect. This turns out to be a rather useful form of bacterial ‘biocontrol’ – there are currently a few products based on lytic viruses approved to control the bacterium Listeria monocytogenes in packaged food products.

The second life cycle is known as the lysogenic cycle. In this phase, the phage integrates into the genome of the bacterium and bides it’s time (referred to as a temperate phage). Think of it as a form of genetic modification of bacteria – when integrated, the genetic information of the phage is replicated along with the genetic info of the host bacterium and so is passed on to the next generation when the bacterium divides. This is one of the mechanisms of horizontal gene transfer, by which bacteria can pick up new genes, for example, encoding new toxins or antibiotic resistance genes. When conditions are right, the phage can become active again, switching back to a lytic lifestyle.

As phage are so abundant, bacteria have developed numerous forms of ‘immunity’ to protect themselves. One of these is called the CRISPR system, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. In this quite elegant system, short segments of foreign DNA, called spacers, are incorporated into the bacterial genome between CRISPR repeats. These spacers serve as a sort of immune ‘memory’ of past exposure. CRISPR spacers are then used to recognise and silence foreign genetic material in a similar manner to RNA interference (RNAi) in eukaryotic organisms.

In a paper just out in Nature (alas, its not open access so here is the write up of it on Science Daily), Tufts University’s Prof Andrew Camilli and his postdoc Dr Kimberley Seed have found that a phage which infects the bacterium Vibrio cholerae, the agent of cholera, has turned the tables on it’s prey, by having its own CRISPR system. It uses its spacers to encode the genetic information for a chromosomal island normally used by V. cholerae to counteract phage. Kimberley showed that phage that were missing the spacer sequences were no longer able to lyse V. cholerae carrying the chromosomal island. This is pretty neat. By possessing its very own CRISPR system, the phage can rapidly adapt to any new weapons in its adversary’s arsenal.

Kimberley D. Seed, David W. Lazinski, Stephen B. Calderwood, Andrew Camilli. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature, 2013; 494 (7438): 489 DOI: 10.1038/nature11927

*According to Wikipedia, the term phage comes from the Greek for ‘to devour’.

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