Moselio Schaechter


  • The purpose of this blog is to share my appreciation for the width and depth of the microbial activities on this planet. I will emphasize the unusual and the unexpected phenomena for which I have a special fascination... (more)

    For the memoirs of my first 21 years of life, click here.

Associate Bloggers



  • (Click photo for more information.)

Bloggers Emeriti


  • (Click photo for more information.)

Meetings & Sponsors



« Living On the Edge…of the swarm | Main | Oddly Microbial: Ribocytes »

April 05, 2012

Wily Phage Trumps Host Toxin

by Merry Youle

Toxic risk flag
Source.

Toxin-antitoxin (TA) systems are a dime a dozen. They are found on plasmids and chromosomes within many prokaryote groups—even those with an intracellular lifestyle. Each is a two-gene operon, one gene encoding a toxin protein, the other the cognate antitoxin. Key to their function is the differential stability of the two gene products, the antitoxin degrading more rapidly than the toxin. When both the toxin and the antitoxin are present in the cell, all is well. They interact and the antitoxin neutralizes the toxin. When production is halted, the toxin outlives the antidote and then kills the cell (or at least inhibits its growth). TA systems carried on plasmids have earned the epithet addiction module. If a host cell jettisons the plasmid, it is dead, thus guaranteeing the maintenance of the plasmid in the host cell lineage.

That these modules are so often carried on bacterial chromosomes suggests they are useful for the bacterium. They have all the makings of an effective defense against phage infection. Here’s why. Typically, an invading phage rapidly shuts down host protein synthesis. If the host carries a TA system, on either its chromosome or a plasmid, cell suicide would quickly follow and phage replication would be thwarted. That particular host cell would die, but in so doing it would protect its siblings nearby by preventing the release of progeny phages.

Two such modules are known that may be used as phage defenses by E. coli. Both are canonical Type II TA systems, Type II being those in which an antitoxin protein binds to and inhibits the action of the toxin protein. The two systems are homologs, but with low sequence similarity. For both, the toxin is an endoribonuclease that degrades cellular (and phage) mRNAs, but each antitoxin is specific for its cognate toxin. One (rnlAB) resides on the chromosome of E. coli K-12, the other (lsoAB) was recently found on a small plasmid isolated from enterohaemorrhagic E. coli O157:H7.

One might expect that both of these TA modules would deter phage T4, but this is not the case. T4 has found a way to keep the host from hacking its DNA into pieces. The secret is its dmd gene. When phage mutants lacking that gene infect E. coli, their mRNAs are chopped and replication halts. If a phage carries the gene, the Dmd protein it makes during infection provides protection by acting as a replacement for the degrading host antitoxin. Dmd has no sequence similarity to the antitoxin made by either of those TA modules, but it can bind to either toxin (LsoA or RnlA) and inhibit their endoribonuclease activity. This promiscuous behavior is a first for the phages, as all other known protein antitoxins are specific for their cognate toxin.

Dmd action

The TA system LsoAB has potential anti-T4 activity. Under normal growth conditions, the toxin (LsoA) and antitoxin (LsoB) proteins are constitutively expressed by the host E. coli and form a complex in which the antitoxin inhibits the action of the toxin (left panel). Following infection by wildtype T4 phage (center panel), the antitoxin protein is degraded. The T4 Dmd protein serves as an alternative antitoxin and inhibits the toxin (LsoA). Infection by a T4 dmd mutant (right panel) also causes the antitoxin to be degraded. The toxin is then free and degrades phage and cellular RNAs, thus preventing phage replication. Source.

This story recently was featured in a MicroCommentary in Molecular Microbiology. The authors there noted that although T4 is one of the best studied phages, we still know nothing about the function of more than a hundred of its ~300 genes. We also are still woefully ignorant of the many factors, in addition to required cell surface receptors, that determine which hosts any phage can successfully infect. In their words: It seems likely that the subtle interactions of specific resistance and counter—resistance mechanisms play a greater role than previously realized— and have a profound impact on the evolution of both phage and host.

ResearchBlogging.org

Otsuka Y, & Yonesaki T (2012). Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Molecular Microbiology, 83 (4), 669-81 PMID: 22403819

Comments

Verify your Comment

Previewing your Comment

This is only a preview. Your comment has not yet been posted.

Working...
Your comment could not be posted. Error type:
Your comment has been saved. Comments are moderated and will not appear until approved by the author. Post another comment

The letters and numbers you entered did not match the image. Please try again.

As a final step before posting your comment, enter the letters and numbers you see in the image below. This prevents automated programs from posting comments.

Having trouble reading this image? View an alternate.

Working...

Post a comment

Comments are moderated, and will not appear until the author has approved them.

Teachers' Corner

Podcast

How to Interact with This Blog

  • We welcome readers to answer queries and comment on our musings. To leave a comment or view others, remarks, click the "Comments" link in red following each blog post. We also occasionally publish guest blog posts from microbiologists, students, and others with a relevant story to share. If you are interested in authoring an article, please email us at elios179 at gmail dot com.

Subscribe via email

Translate




Search




MicrobeWorld News

Membership