The fly, the amoeba, and the worm

The fly, the amoeba, and the worm

Robet Koch formulated in 1890 the Koch´s postulates as general guidelines that should be followed to identify pathogens causing diseases. One century later, Stanley Falkow established the molecular version of Koch's postulates to guide, this time, the identification of microbial genes encoding virulence factors. A key point of the molecular postulates is to test the virulence of the microorganism with the inactivated candidate virulence gene in an appropriate animal model. However, this is not always possible. Suitable animals models are lacking for many diseases such as brucellosis, typhoid and leprosy. And the models for tuberculosis and cholera do not reflect the biology of human infections. In addition, large scale analysis of virulence are costs prohibited due to the high number of animals that should be infected to get statistically significant results. And, last but not least, there are important ethical concerns on the use of vertebrate animals models (including mice and rats) for research. In the case of plant pathogens ethical concerns are not an issue, however the logistics behind a virulence experiment in plants represent a challenge (space, biosafety regulations, possibility of spreading in nature of genetically modified organisms,...).


To solve these issues, some years ago new models to test virulence were introduced: Drosophila melanogaster (the fruit-fly), Dyctiostelium discoideum (the social amoeba) and Caenorhabditis elegans (the soil nematode). With general skepticism, it was assumed that the same virulence factors important for virulence in humans/plants could play a role in the interplay with these surrogate hosts. Indeed, this has been case, and these three amigos (no offense for the actors, I like the movie) have made outstanding contributions to the microbial pathonegesis field.

P4 infectious diseases medicine

The XXI century has brought a new concept to Medicine, the P4 medicine, term coined by Leroy Hood. More than a new concept, P4 medicine should be considered as a new way to approach medical care. The vision of P4 medicine —shorthand for predictive, preventive, personalized and participatory medicine— is that instead of waiting until the patient is sick before responding, physicians will be able to detect early warnings of disease to take early action and people may even be able to adjust their lifestyles to prevent disease. To make P4 medicine true it is essential a broad interdisciplinary approach including methods for personalized genome sequencing and new computational techniques for building dynamic and disease‐predictive networks from massive amounts of data from a variety of OMICs. In other words, the heart of P4 medicine is to define new methods for interrogating and understanding the interaction between the environment and the genome of the individual. 

There are already P4 medicine successful stories. An excellent example of the effectiveness of this approach is the change in cancer treatments. Nowadays, emphasis is placed on early detection, followed by genotyping of the patient to use the most adequate treatment according to the genetic background. Cardiovascular diseases and perhaps even neurodegenerative disorders will be the next targets for P4 medicine. However, what about infections? Can we apply the P4 medicine approach to infectious diseases? In my view, yes.

* Recently I have published a review based on this blogpost in the June 2012 issue of International Microbiology, the flagship journal from the Spanish Microbiology Socitey (SEM).

Bacteria: nanotech freaks

Nano dimension: graphene cells

Nanotechnology is considered the next "miracle potion" specially if you add the bio term: nanobiotechnology. However, it only refers to the possibility of working at the molecular sclae (100 nanometers). New materials have been created and there are already a lot of promising nano methods that will help to diagnose and treat diseases faster and perhaps even better than before. But, like many other times, we are just re-discovering the wheel. Biological systems are inherently nano in scale. Actually, all living things, including humans, can be considered as nanofactories. Evolution has optimized these nanofactories over millions of years and just now, in the 21st century, we are tapping into this nano-world. 

Who are the experts on this field? The first ones on the ranking are not renowned scientsits but... pathogenic microorganisms. Viruses and bacteria use the most sophisticated nanotools to subvert the machineries of cells to survive. Prominent examples are the systems used by viruses to inject DNA into cells or the systems that bacteria employed to deploy proteins into cells, chiefly the so-called type III secretion systems (T3SS).

2011 Nobel Prize in Medicine: a tribute to endotoxin research!

J. Hoffmann, B. Beutler, R. Steinman

Finally I got the Nobel Prize!! Actually, innate immunity, my research topic, got the prize.  The innate immune system is the main weapon that keeps organisms without infections. A proof-of-concept example is the pioneering work carried out by Jules Hoffmann´s team showing how fruit flies combact infections. Their work led to the identification of the receptor, named Toll, used by the flies to detect pathogens. A similar receptor, called Toll-like receptor (TLR) 4, turned out to be expressed by our cells and its activation cause inflammation, an essential response to eliminate invading microorganisms. Bruce Beutler´s studies using knock-out mice made an elegant clear-cut case. However, we should not forget that the work and insights of Charles Janeway were the driving force for this line of research. World-class scientists continuing his fundamental work are Ruslan Medzhitov, Shizou Akira, Douglas Golenbock, Terje Espevik, Luke O´Neill,...just to mention a few. However something is missing...A dogma in Biology is the receptor-ligand notion. In other words, there is always a ligand, at least one, for a given receptor. Let´s put in Nobel Prize context decades of outstanding research on the TLR4 ligand: the lipopolysaccharide.

The circle of science

"There's more to see than can ever be seen
More to do than can ever be done
There's far too much to take in here
More to find than can ever be found"

Many of you know this part of the lyrics of "The lion king". I think it reflects nicely the driving force of most scientists that I know, or at least my own. Actually, I like to think that I continue the line of those famous explorers of the the last centuries: Stanley, Amundsen, Sarmiento de Gamboa, Magallanes,...jut to mention a few. It may sound a bit pretentious. However, at a reduced scale, I believe that my excitement when opening the incubator to check the outcome of the last experiment after an overnight incubation is similar to the feelings of those great explorers when reaching the end of the journey. I enjoy the daily life at the lab, even the small things: when a cloning is done or when we construct a new bacterial mutant lacking a, hopefully, new virulence factor. But it is a long, tough, dificult process to get to this situation. I will leave for another post the description of the so-called "scientific career". Instead, for those not familiar, I will summarize here the whole process of "doing science". 

Antibiotics resistance: when enough is enough!

There is a general concern on the spread of bacteria resistant to antibiotics. The scientific community is well aware of the problem already since the isolation of Staphylococcus aureus resistant to methicillin (MRSA) in the late 1990s. The list of bacteria resistant to virtually all drugs is increasing nearly every month and the top ten killers superburgs include Pseudomonas, Acinetobacter, Clostridium, Mycobacterium, Enterococcus and Klebsiella. The general public is also aware of the increasing isolation of multidrug resistant bacteria since it makes often headlines at the news. However, I should say that their awareness is not enough. Public and mass media maybe missing the big picture: in the XXI century patients are dying in our hospitals due to the lack of treatments for infections.

A new kid on the block

I guess that most of you know that the name of the blog, cést les microbes, is one of the quotes of the famous French microbiologist Louis Pasteur, the father of Microbiology. It took me a while to decide it. But at the end, one should go back to the clasiscs. The name stands alone and actually suggests what you will find here: posts about Microbiology considered in a broad sense. I will comment on antibiotics, infection biology, innate immunity, viruses,...pretty much my research interests.

I strongly believe that one of my duties as a scientist is to disseminate my knowledge to the public. So actually this a key point of this blog: I am an active scientist and not a journalist who write about science. Therefore, in this blog you will find expert posts written in layman terms but always accurate and avoiding sensacionalism. Further, the posts will not be a summary of recent papers but instead will reflect my view on the topic aiming to generate feedback (discusion) from your side. So please leave always a comment!!