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



« Talmudic Question #65 | Main | Making it Personal »

September 06, 2010

Listeria's Visiting Card

by Elio

Listeria-monocytogenes(4)

Listeria monocytogenes (Scanning EM). Source.

During infection, host and parasite carry out repeated and intense conversations that often rise to the level of shouting matches. The language they use is chemical, the words and sentences eloquent and forceful. Eavesdropping on the conversation between Listeria monocytogenes and immune cells of its host, Portnoy and colleagues discovered an intriguing linguistic use for a novel “second messenger,” cyclic-di-AMP (c-di-AMP).

It has been known that Listeria, like many intracellular pathogens, promotes the making of an interferon (IFN-β), which in turn signals cells of the immune system, thus activates them. But what sets this in motion? What are the signals emitted by Listeria and how are they “heard” by the host cells? The answer is that the bacteria excrete c-di-AMP, which activates the so-called cytosolic surveillance pathway. One aspect of this is the making of interferon. The immune response is now off and running; mobilized killer lymphocytes and other host defenses ward off the invading organisms.

C-d-AMP
Cyclic-di-AMP. Source.

The bacteria must be alive for this kind of immune system activation. How come? It turns out that live Listeria, like other bacteria, have powerful, multidrug efflux pumps, usually thought to be there to get rid of harmful compounds such as antibiotics. But these pumps function here to secrete a constituent of the bacteria themselves: c-di-AMP. Such secretion is harmful to the bacteria because they now have to cope with the consequences of having elicited powerful host defenses. Makes you wonder how come it was not selected against and what else is going on with this story. Nevertheless, here it is, another case where the invading agents announce their presence to their own detriment. (In the words of Lewis Thomas, bacterial lipopolysaccharide is just such a “visiting card.”)

How did the investigators make this discovery? Observing Listeria mutants with multidrug efflux pumps with varying levels of activity, they found that the amount of interferon made correlates with pump activity. This suggested that induction of interferon production was due to a secretable, relatively low molecular weight compound. So, they fractionated culture supernatants and identified the active compound as c-di-AMP. Store-bought c-di-AMP works the same way and in a dose-dependent fashion. What is novel and exciting here is that this cyclic nucleotide works outside the bacterium. Such signaling molecules are supposed to work within the cell that makes them. For a discussion on the secretion mechanisms of virulence factors, see a review by Vance, Isberg, and Portnoy.

Like Listeria, many other Bacteria and Archaea also have proteins with a c-di-adenylatecyclase domain, the active domain thought to make our favorite cyclic dinucleotide. In B. subtilis, this domain is part of a protein called DisA (DNA integrity scanning protein A). Interestingly, DisA is said to have a role in sporulation by monitoring DNA damage at the beginning of the process. DisA molecules are seen in intracytoplasmic foci that move inside bacterial cells, apparently scanning the DNA as they go, to detect the presence of lesions. This seems totally unrelated to the Listeria story, but it indicates that c-di-AMP may play a role elsewhere. Just what it might be doing in Listeria or other bacteria is a mystery. This is surely not the end of the story. c-di-AMP’s cousin, c-di-GMP, is getting a lot of play as a regulator, so we can put our money on the discovery of further roles of cyclic dinucleotides.

There may be also a practical aspect to this discovery. If Listeria has developed into such a powerful immunogen, might one not exploit it for making better vaccines? The Portnoy lab is giving this a good try and we will report of any progress they or others make along these lines.

ResearchBlogging.org

Woodward JJ, Iavarone AT, & Portnoy DA (2010). c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science (New York, N.Y.), 328 (5986), 1703-5 PMID: 20508090

Comments

Hi Mark,

try this reference describing chemiluminescence due to superoxide dismutase in human macrophages exposed to killed S. aureus:

www.ncbi.nlm.nih.gov/pmc/articles/PMC421090/pdf/iai00211-0127.pdf

Prometheus sounds like a good analogy there...but Icarus may be as relevant for those bacteria getting too close to UV sources.

Say, Richard----can you chase me down a reference on macrophages generating light upon an oxidative burst? If you are too busy (isn't everyone?), I'll keep looking.

Makes me think about a lot of issues involving light, and Prometheus....

Fascinating article. L. monocytogenes is an intracellular pathogen and uses listeriolysin (among other techniques) to disrupt the phagolysosome when ingested into macrophages allowing it to survive in the cytosol where it can replicate. Seems like the immune attractant may serve some evolutionary purpose as bait for unwitting macrophages! Incidentally, I wouldn't be surprised if L. monocytogenes has light sensitive metabolic shift like Brucella abortus which also is intracellular for macrophages ( macrophages emit light when undergoing oxidative burst).

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