Hello, hello. You’re now tuned to your favorite blog: micro-writers.egybio.net. Tonight we have this very special guest, live, online. After two months of waiting, we finally got this exclusive interview with the emerged Streptococcus pyogenes strain, the most dangerous ever, M1T1. We have it here, with us, in the studio.

– Hello, M1T1. Welcome in our studio.Streptococcus pyogenes - Adopt A Microbe
– Hey there.

– We knew from our resources, which are totally classified, that you got yourself in trouble recently.
– (Interrupting), I did NOT get myself in trouble. EID set me up.

– M1T1, Would you please calm down & tell us a little more about yourself?
– Well, I belong to Group A streptococci (GAS) aka Streptococcus pyogenes. M1T1 is my serotype; I’m just a clonal strain. As you know, S. pyogenes colonize human skin & throat causing either non-invasive (sore throat, tonsillitis & impetigo) or invasive (necrotizing fasciitis NF, scarlet fever & streptococcal toxic-shock syndrome STSS) infections. Actually, NF gave me my nick: Flesh-eating bacteria.

– So, you cause all people NF & STSS?
– No, kid. It depends on their genetic susceptibility, what you call “Host–pathogen interactions”. I was isolated from patients with invasive as well as non-invasive infections during 1992–2002. This is NOT entirely my fault; humans can make me extra virulent by selecting the most virulent members.

– Back to your history, when have you exactly been isolated?
– M1 & her sisters were the worst nightmare in US & UK in the 19th century as they caused the famous pandemic of scarlet fever. “Nevertheless”, early 1980s was the golden age of my strain as well as my very close sisters M3T3 & M18. We caused STSS & NF in different parts of the world. Great times, great times!

– Only for you, I suppose! So, what made you hypervirulent? What caused you this “epidemiologic shift”?
– Two reasons Dr Ramy K. Aziz identified that improved my fitness to humans: the new genes I got from phages & “host-imposed pressure”. Both resulted in the selection & survival of me M1T1 the hypervirulent strain. Dr Aziz’s work at Dr Kotb’s lab resulted in identification of a group of genes I got from phages that changed my entire life.

– Interesting! Tell us more about that. How did phages “change your life”?
– Dr Aziz proved that I differ from my ancestral M1 when he found that I have 2 extra prophages (lysogenized phages didn’t get the chance to lyse me, so they became integrated in my genome):
1. SPhinX which carries a gene encodes the potent superantigen SpeA or pyrogenic exotoxin A (scarlet fever toxin).
2. PhiRamid which carries another gene encodes the most potent streptococcal nuclease ever, Sda1.
3. He also found that phages conversion from the lytic state to the lysogenic state resulted in exchange of toxins between our different strains (aka Horizontal Gene Transfer). Phages are very good genetic material transporters, what makes “strains belonging to the same serotype may have different virulence components carried by the same or highly similar phages & those belonging to different serotypes may have identical phage-encoded toxins.” What a quote from Rise and Persistence of Global M1T1 Clone of Streptococcus pyogenes.

– Well, It was not that interesting. So, what? What’s the significance? How that made you hypervirulent?
– You can’t get it? You’re not that smart, are you? Tell me, what made M1 hypervirulent causing scarlet fever in the 1920s and me hypervirulent causing STSS in the 1980s with a 50-years decline period?

– Superantigen?
– Exactly. You do have your moments! Superantigen encoding-gene was present in us and absent in strains isolated in the period between them. The interesting part, for me of course, that humans after 50 years of absence of hypervirulent strains had absolutely no superantigen-neutralizing antibodies. That was the real invasive party. Superantigen causes high inflammatory response because of its non-specific binding to immune system components (antibodies & complements) causing an extremely high inflammatory response. In fact, SuperAg inflammatory response is “host-controlled”.

– So, what about Sda1?
– Streptodornase (streptococcal extracellular nuclease) helps me to degrade neutrophils that entrap me in the neutrophil extracellular traps (NETs). So, I can invade humans freely & efficiently and be able to live in their neutrophils. Dr Aziz proved in his paper “Post-proteomic identification of a novel phage-encoded streptodornase, Sda1, in invasive M1T1 Streptococcus pyogenes” that it’s all about C-terminus in my Sda1; the frame-shift mutation increased my virulence while deletion decreased it.

– Now we know about your SuperAg & nuclease (DNase), what’s the “host-imposed pressure”?
– I have my own SpeB (Protease), I use it to degrade my other proteins (virulence factors), which provides me with a good camouflage & gives me access to blood. When the host immune system recognizes me, it traps me in NETs. At this time, I secret Sda1 to degrade neutrophils. Actually, SpeB protects you, humans, from my Sda1& my other toxins. When SpeB was compared in patients with severe & non-severe strep infections, it was found that SpeB wasn’t expressed in case of severe infection. Expression of SpeB may be host-controlled, as host selects the mutants with a mutation in covS, a part of my regulatory system which regulates my gene expression including SpeB gene.

– Finally, M1T1. How do you see your future?
– More new phage-encoded genes, more selection of the hypervirulent strains by the host & more regulation of expression of my virulence factors. Pretty good future! I also count on humans to not develop immunity against me like what happened in 1980, when I got new virulence factors or allelic variations in my old ones.

Thank you, M1T1. Pleasure talking to you…….M1T1? M1T1, where are you? Why do I feel this strange pain in my throat?

Image credits:
Streptococcus pyogenes: http://adoptamicrobe.blogspot.com/

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5 Responses to “M1T1: Exclusive Interview”
  1. Nice Topic… Great Idea… 🙂

  2. Declaration of conflict of Interest.

    Although this is only a blog post and not a scholarly article, I am obliged to post the following declaration of conflict of interest. The post mentions parts of my research work, but I was against the publication of such a post in this blog. The reason is that I have initiated this blog and that I own and administer the web sites. This may represent a conflict of interest, and I would love to have it clarified to every reader by me rather than by anybody else.

    In addition, while this blog post mentioned accurately parts of my research work, it failed to acknowledge other similar work in the field, which would give some uninformed readers the impression that the discovery of the M1T1 phages was solely made by our research group. This is not the case. First of all, the findings mentioned in this blog post were the result of an ongoing collaboration between different laboratories, notably the laboratories of Drs. Mark Walker (in Wollongong, Australia) and Victor Nizet (in San Diego, USA). Also, phages have been known to contribute to streptococcal virulence since the early XXth century. The presence of phages that differentiate M1T1 from ancestral strains was described by Cleary et al. years before we sequenced these phages. Sumby and coworkers also sequenced an entire M1T1 strain, MGAS 5005 and found similar findings that were published few weeks after our study. The same can be said about the streptodornase story.

    Ramy K. Aziz, Lecturer, Department of Microbiology and Immunology, Cairo University

  3. Three months since the “launch” started. Three months of reading, writing & reviewing, it never happened that an author left his comment for us. Authors just kept shooting in & out to know who’s linking their articles & when they realize that it’s a students’ blog, they simply dump it coz it’s absolutely nothing for them.
    Micro-writers has been honored twice, the first time was when it reviewed your article & the second time was when you left your clarifying comment for the Micro-readers.
    As the author of the post, I admit that I was aware of the conflict of interests before publishing the post. But I’m reviewing a micro-article like any other post on Micro-writers. Talking about myself, I prefer to focus on a main article (specially reviews) & link other articles to it if necessary & a quick look at my previous posts will support my talk.
    You taught us not to talk about a research group like they’re :”The League of Extraordinary Gentlemen”, just state facts. I guess that’s what I did.
    Again, none of the authors we’ve reviewed their articles left us a comment. So, thank you Dr. Ramy for the comment.

  4. Well, again, I’m not really a random “author,” so the comparison is unfair. It’s also hard to assume that “authors just kept shooting in & out to know who’s linking their articles & when they realize that it’s a students’ blog, they simply dump it coz it’s absolutely nothing for them.” If a visitor’s IP address coincides with an author’s institution, it still could be one of their students, their administrators, their department’s press advisors, etc…

    Here is aninteresting article I stumbled upon.

  5. Hi, nice blog – you have some cool articles here, I enjoyed reading them! Glad I am not the only one furthering the microbiology cause on the internet. I have written about fleshing eating strep on my site too, although your post is far more informative! http://ilovebacteria.com/streptococcus.htm
    Keep up the good work!

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