Is it a luxury to “think like a microbe” and to publish blogs such as “Adopt a Microbe“ and books like “The Other End of the Microscope: the Bacteria Tell Their Own Story“ (find it on Google Books)? Is it just about understanding or “getting to know” bacteria, or is it a necessity to be “microbe-oriented” for better understanding of pathogenesis and for developing the appropriate eradication and prevention strategies (I can’t think of better examples other than Reverse Vaccinology and H. pylori)?

When I first read this commentary “The Case for Biocentric Microbiology”* by Dr. Ramy Aziz, published by the journal “Gut Pathogens, I was shocked! The article was presenting a very different perspective, at least different from what I always dreamed of as a pharmacy student, to kill the bad bugs by designing an effective, highly selective chemotherapeutic! Plus it was my first time to read an opinion article, and I used to take the microbiology courses for granted; “this is a bad microorganism, causing this bad infectious disease with serious manifestations including these, diagnosed by the following and the antibiotic of choice is this.” And then Dr. Aziz came with this article with the cool, simple and exciting writing style that keeps one alerted the entire article, gathering all those thoughts and examples of our human-centered/self-centered view of microbiology.

Four parts I enjoyed the most in the commentary:

• The tabular form of “differences between the anthropocentric and biocentric views of microbes.”
• The final balancing paragraph –the conclusion.
• The “competing interests” part, which is funny.
• The questions part, which is an excellent idea to open up discussions, especially for those who are not-natural-born brain stormers like me!

Even though microbiology is a new science, it suffers from anthropocentric view that Galileo suffered from; starting with the field’s name itself, “microbiology” -liked what Dr. Elio Schaechter mentioned: “Small,” says who? Not the microbes… till the funding agencies that give priority to studying bad microbes (i.e., pathogens), and good microbes (i.e., fuel-producing and yogurt-making bacteria) nothing else!

We, in our human-centered view; automatically classify any newly-discovered bacterium to fall into one of three categories: the good, the bad and the ugly… no, not that one! They are: the useful guys, the harmful guys and the just-existing guys. Now, let’s take a look at the biocentric view of microbes: Humans and microbes share many ecosystems. To microbes, humans are just an ecosystem that is a “relatively safe” habitat with a source of nutrition.

As victims, we think about pathogenesis/infection as it’s shedding from the immune system, invasion and toxin production; but microbe-oriented microbiologists/bacteria whisperers know that, to bacteria, pathogenesis is  just defense, seeking nutrition, and excretion of metabolic byproducts. Being pathogenic or opportunistic is not their reason of existence, it’s just a form of adaptation to survive in this hostile environment (aka the human body).

You do not believe me!? OK, bacteria lived –happily- thousands of millennia before mammals and humans, so their reason of existence can’t be to harm humans, like what Dr. Aziz is mentioning: “Who attacks whom”, are the bacteria the “one” that start the fight, or is it the human immune system that starts the war against them?  A very interesting example to understand adaptation is Legionella pathogenesis, and how they adapted to human macrophages because they used to survive in amebas, which are similar to our macrophages.

Back to the basic question, is it a luxury or a necessity?

Studying “all” bacteria from their perspective will help us in understanding pathogenesis and subsequently developing strategies to combat infectious diseases (immunization and design highly selective chemotherapeutics), will give us a better idea of the tree of life and the metabolic map, and studying environmental microbiology will allow us to meet new “useful” microbes like what happened with the PCR Taq-polymerase, we knew how to make use of this bacterial polymerase that can work at those very high temperatures required for the PCR steps.

Here are two interviews about the commentary covering two segments of readers, the first one is with Dr. Betsey Dyer, Professor of Biology at Wheaton College, and the second one is made with Radwa Raed, a micro-writer and a final-year FOPCU student:

1- What is your opinion about (the commentary)? To what extent do you find it compatible with your bacteriocentric view of bacteriology? How strong are the arguments?

Dr. Betsey D. Dyer, Professor of Biology at Wheaton College.

“I thoroughly enjoyed Ramy Karam Aziz’s article “The Case for Biocentric Microbiology.” I think he is absolutely right that some old fashion thinking about the divisions of microbiology and anthropocentrism in general have hindered a more complete understanding of the microbial world. I also think Dr Aziz is quite bold and daring. I’m not sure I could have gotten such forceful statements accepted for publication! Good for “Gut Pathogens” to print it! I hope Dr Aziz gets lots of readers and citations.”

2- How did (the commentary) change your point of view? Are you with or against the biocentric view for microbiology? Do you think about it as a view against, or at least far from, your beliefs as a pharmacy student dreaming of fighting diseases? What are your opinions regarding studying environmental microbiology in pharmacy school?

Radwa Raed, Pharmacy student, Faculty of Pharmacy, Cairo University – Egypt.

“From my humble point of view, I would have to agree (with the biocentric view of microbiology). It goes without saying that studying more about certain bacteria “the ones some would consider to be of the least priority” will definitely expand our knowledge about the overall, and in many cases analogous or even similar, methods of survival, adaptation to existing conditions, etc.., which all pretty much ultimately serve medical microbiology. Plus, leaving a whole chunk, simply unexplored, can only raise several “what if” questions; one of which, that comes to mind, is what if the simplicity and less dramatic forms of life could help researchers better grasp the machinery behind these fascinating little creatures 🙂

As for studying environmental microbiology in pharmacy schools, I would have to oppose the idea, because the field of pharmaceutical science is taught so the future students can come to understand, and hopefully later suggest, treatment methods against pathogenic microorganisms, prophylaxis, and so forth..so studying the harmless ones would not point in this direction. It can only lead them to drift away from the pharmaceutical science branch of study into a more microbiology-oriented career.”

You can read the paper, share your comments and debate the arguments here, and you can also vote for it on BioWizard.

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*Full Citation:

Aziz, R. (2009). The case for biocentric microbiology Gut Pathogens, 1 (1) DOI: 10.1186/1757-4749-1-16

Tags: adopt a microbe, anthropocentric, bacteriocentric, Betsey D. Dyer, biocentric microbiology, commentary, competing interests, environmental microbiology, gut pathogens, H. pylori, metabolic map, microbe-oriented, microbiology, pathogenesis, pathogens, PCR, Ramy K. Aziz, reverse vaccinology, taq-polymerase, the case for biocentric microbiology, the other end of the microscope, tree of life

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.
– 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 19^th 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/

Tags: covS, epidemiologic shift, flesh-eating bacteria, global M1T1 clone, group A streptococci (GAS), horizontal gene transfer, host-imposed pressure, host–pathogen interactions, impetigo, M1T1, Malak Kotb, necrotizing fasciitis, neutrophil extracellular traps (NETs), phage-encoded toxins, pyrogenic exotoxin A, Ramy K. Aziz, S. pyogenes, scarlet fever, sore throat, streptococcal nuclease Sda1, streptodornase, STSS, superantigen SpeA, tonsillitis