|Ibrahim, Ashraf - UCLA|
|Gebremariam, Teclegiorgis - UCLA|
|Liu, Mingfu - UCLA|
|Chamilos, Georgios - MD ANDERSON CANCER CTR|
|Kontoyiannis, Dimitrios - MD ANDERSON CENCER CTR|
|Mink, Richard - UCLA|
|Kwon-Chung, Kyung - NIH|
|Fu, Yue - UCLA|
|Edwards JR., John - UCLA|
|Spellberg, Brad - UCLA|
Submitted to: Journal of Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 6, 2008
Publication Date: October 1, 2008
Citation: Ibrahim, A.S., Gebremariam, T., Liu, M., Chamilos, G., Kontoyiannis, D.P., Mink, R., Kwon-Chung, K.J., Fu, Y., Skory, C.D., Edwards Jr., J.E., Spellberg, B. 2008. Bacterial Endosymbiosis is widely present among Zygomycetes but does not contribute to Mucormycosis pathogenesis. Journal of Infectious Diseases. 198(7):1083-1090. Interpretive Summary: It was recently discovered that environmental isolates of the fungus Rhizopus are frequently associated with a symbiotic bacterium, Burkholderia, which lives inside of the fungus and produces a toxin called rhizoxin. This discovery raised the possibility that the presence of the toxin producing bacterium could be involved in the pathogenicity of Rhizopus infections, since rhizoxin can lead to cell death. Twenty eight strains of Rhizopus and related fungi were tested for the presence of bacterial DNA. More than half of the strains tested positive, with 33% of these belonging to the Burkholderia family of bacteria. Additionally, rhizoxin was identified in extracts made from these fungal strains. However, fungi with or without endosymbiotic bacteria did not differ in their ability to cause cell injury in tissue culture assays. Nor did antibiotic-mediated eradication of bacteria and rhizoxin production decrease the virulence of fungal strains in tests using mice or flies. In summary, while bacterial endosymbiosis is widely detected in Rhizopus and related fungal strain, we found no evidence that bacterial endosymbionts and rhizoxin contribute to pathogenesis.This work helps advance our understanding about the ability of Rhizopus to infect certain individuals, which is important because of the widespread use of this organism in both the food and fermentation industry.
Technical Abstract: Environmental isolates of the fungus, Rhizopus, have been shown to harbor a bacterial endosymbiont (Burkholderia) that produces rhizoxin, a plant mycotoxin. We sought to define the role of endosymbiont rhizoxin production in the pathogenesis of mucormycosis. Endosymbiotic bacteria were identified by PCR in 15 of 28 (54%) clinical isolates of Zygomycetes with 33% of the bacterial strains showing >87% identity with Burkholderia 16S rDNA. The presence of rhizoxin in myclial extracts from fungi harboring bacteria was confirmed by HPLC analysis. However, fungal strains with or without endosymbionts did not differ in their ability to cause endothelial cell injury in vitro. Nor did antibiotic-mediated eradication of endosymbionts and rhizoxin production decrease the virulence of fungal strains in mice or flies. In summary, while bacterial endosymbiosis is widely detected in clinical isolates of zygomycetes, including R. oryzae strains, we found no evidence that bacterial endosymbionts and rhizoxin contribute to mucormycosis pathogenesis.