Thaxtomin, a next-generation weed killer ?

It is called “Streptomyces scabies”. This bacterium is feared by farmers because it causes common potato scab, a disease which despite being harmless causes distasteful lesions to appear on tuber crops. And yet this bacterium could become a micro-scale helper for these same farmers because the toxin it produces, thaxtomin, is a natural and biodegradable herbicide which is to date unfortunately too expensive to produce on a grand scale. Two researchers at the Center of Protein Engineering at the University of Liege, Sébastien Rigali and Samuel Jourdan, in collaboration with Dr. Isolde Francis and Professor Rosemary Loria of the University of Florida, have just discovered the molecular mechanism responsible for inducing the synthesis of this toxin. Their discovery forms the basis of a patent proposal whose objective is to make thaxtomin as a commercially viable natural herbicide.

Potato common scabThe appearance of these bacteria is not their strong point. Causing brownish scab lesions on all or some of the skin of tubers they do not look very appetizing. Even the name of the disease is enough to cause disgust. After all, who would want to eat potatoes affected by common scab?

Yet despite the unsavory appearance and name of the disease affecting these potatoes, they are not unsuitable for consumption. However, in our societies where appearance counts, we rarely find tubers affected by the disease on sale in supermarkets. This is a great pity considering the staggering losses that the removal of these tubers from supermarket shelves can cause. In Canada, in 2007, researchers estimated annual losses related to the disease at between 15 and 18 million dollars. No data is available for Belgium but common scab has no borders...

The main causative agent of this disease is a bacterium called Streptomyces scabies. It is the black sheep of its family in some respects: among the hundreds of different species of Streptomyces, the latter is one of the rare pathogenic members, that is to say, capable of causing disease in the plant concerned. The potato is not its only victim; it also affects carrots, beetroot, turnips and radishes... It is somewhat out of tune with its many “cousins” which by way of contrast are reputed for their beneficial effects. They are, in fact, the source for more than half of the natural antibiotics, anticancer, antibacterial and antifungal products used in human medicine or in the agriculture industry.  

The tip of the iceberg

It is no surprise that these Streptomyces should be in the sights of Sébastien Rigali and Samuel Jourdan, both of whom are researchers at the Center of Protein Engineering (C.I.P.) at ULg. “Our focus in the laboratory is to understand when, how and why these bacteria produce a molecule that has an antibiotic activity, the meaning of antibiotic being ‘against life’: against viruses, bacteria, plants, fungi, etc. The purpose of this is to find new antibiotics. We now know that the 10,000 molecules of Streptomyces that have been isolated to date are merely the tip of the iceberg! Genome mining has revealed the existence of numerous ‘cryptic’ antibiotics, that is to say, they are unknown because they are not produced under laboratory culture conditions. The genes coding for the proteins that synthesize these cryptic molecules are often ‘silent’, that is to say barely expressed or not at all. The key to unlocking the system must be found. These keys are the transcriptional regulators, proteins that are capable of repressing or activating the expression of genes”.

Scientists have been tirelessly attempting to identify the keys and locks involved in the expression of the genes involved in the production of antibiotics. Once the lock-and-key systems have been decoded, it becomes possible to identify the elicitors of the system, that is to say the triggering elements which, in their natural environment, cause the bacteria to produce these cryptic antibiotics. You might as well be looking for a needle in a haystack given the infinite number of lock-and-key combinations and elicitors that exist!  

At ULg, in direct collaboration with the Universities of  Leiden (NL) and Erlangen (DE), Sébastien Rigali  was the first, in 2008, to identify a complete signaling cascade (keys, locks, and elicitor) in Streptomyces coelicolor, from the extracellular perception of a signal to its transformation into a decision-making role: the production of an antibiotic (1). Since then, the researchers in the ‘Streptomyces Genetics and Development’ group of C.I.P. have been trying to repeat this for other Streptomyces. To succeed, they plan to adopt a bioinformatics approach by using the PREDetector program (2) which makes it possible to detect the ‘locks’ involved in gene expression. Once these locks have been detected, it will be easier to find the key and then identify the environmental elicitor for the system.

(1) Rigali S, Titgemeyer F, Barends S, Mulder S, Thomae AW, Hopwood DA, van Wezel GP. 2008. Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO reports 9:670-675.
(2) Hiard S, Maree R, Colson S, Hoskisson PA, Titgemeyer F, van Wezel GP, Joris B, Wehenkel L, Rigali S. 2007. PREDetector: a new tool to identify regulatory elements in bacterial genomes. Biochemical and biophysical research communications 357:861-864

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