Illuminating virulence

The advent of molecular methods made necesary to revise the Koch´s postulates, formulated in 1890, as general guidelines that should be followed to identify pathogens causing diseases. As a result, Stanley Falkow established the molecular version of Koch's postulates to guide the identification of microbial genes encoding virulence factors. Falkow established five experimental criteria that a gene must fulfill to be considered a virulence factor. A criterium almost never addressed by scientists is "The gene, which causes virulence, must be expressed during infection." It has been always considered enough to test whether specific inactivation of the gene is associated to a measurable loss of virulence. Actually, the golden standard is to demonstrate in vivo (using suitable animal/plant models) that allelic replacement of the mutated gene leads to restoration of virulence.

However, wouldn´t it be interesting to know exactly when and where the virulence gene is expressed? Certainly this may help to understand the in vivo role of the virulence factor: is it required only for the initial colonization of the tissues? Is it necesary to fight phagocytic cells?, is the expression of this factor coordinated with those of other factors?,...Moreover, are there virulenece factors expressed only in vivo and therefore absolutely dispensable in vitro? These questions led scientists to develop experimental approaches to enlighten virulence gene expression. Conceptually, the methods were originally conceived upon the premise (now considered fact) that most virulence genes are transcriptionally induced at one or more times during infection

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.