Pathogenic fungus harbours endosymbiotic bacteria for toxin production

The antitumour agent rhizoxin is a fungal metabolite produced by Rhizopus microsporus, the pathogen that causes one of the most destructive diseases of rice crops, rice seedling blight. Or so we thought. Now it has been discovered that Rhizopus is not the true producer of rhizoxin. In fact it is synthesized by a bacterium of the genus Burkholderia, living in the fungus as an endosymbiont. Rhizoxin causes cell-cycle arrest in the plant cells, and the fungal pathogen and its symbiont both benefit from the decaying plant matter produced. A number of plant pathogenic fungi belonging to the genus Rhizopus are infamous for causing rice seedling blight. This plant disease is typically initiated by an abnormal swelling of the seedling roots without any sign of infection by the pathogen1,2,3,4. This characteristic symptom is in fact caused by the macrocyclic polyketide metabolite rhizoxin that has been isolated from cultures of Rhizopus sp.5,6. The phytotoxin exerts its destructive effect by binding to rice β-tubulin, which results in inhibition of mitosis and cell cycle arrest7,8. Owing to its remarkably strong antimitotic activity in most eukaryotic cells, including various human cancer cell lines, rhizoxin has attracted considerable interest as a potential antitumour drug9,10. Here we show that rhizoxin is not biosynthesized by the fungus itself, but by endosymbiotic, that is, intracellular living, bacteria of the genus Burkholderia. Our unexpected findings unveil a remarkably complex symbiotic-pathogenic relationship that extends the fungus–plant interaction to a third, bacterial, key-player, and opens new perspectives for pest control.