TY - JOUR
T1 - The innate immunity of maize and the dynamic chemical strategies regulating two-component signal transduction in Agrobacterium tumefaciens.
AU - Maresh, Justin
AU - Zhang, Jin
AU - Lynn, David G.
PY - 2006/4/25
Y1 - 2006/4/25
N2 - The naturally occurring 2-hydroxy-4,7-dimethoxybenzoxazin-3-one (HDMBOA), essentially the sole component of maize seedling organic exudate, was shown to be a potent inhibitor of the VirA-VirG two-component system which mediates host recognition and activates virulence gene transcription in the soil pathogen Agrobacterium tumefaciens. The hydrolytic lability of HDMBOA creates a steady-state zone of inhibition circumscribing the young maize seedling. We now show that rather than the HDMBOA natural product, an o-imidoquinone decomposition intermediate, (3Z)-2,2-dihydroxy-N-(4-methoxy-6-oxocyclohexa-2,4-dienylidene)acetamide, can function as an inhibitor of virulence gene expression in A. tumefaciens. Structural characterization of this o-imidoquinone intermediate clarifies several issues related to the decomposition pathways available to this class of antibiotics. Of direct ecological importance, this species is produced rapidly and quantitatively within the more neutral pH ranges of the A. tumefaciens cytoplasm, while HDMBOA is more persistent at the slightly acidic pH common to many soils. These results suggest the rather intriguing possibility that the physical instability of the benzoxazinone antibiotics may not only create a steady-state local defense, but also enable a "pro-drug" strategy directed against bacterial environmental sensing.
AB - The naturally occurring 2-hydroxy-4,7-dimethoxybenzoxazin-3-one (HDMBOA), essentially the sole component of maize seedling organic exudate, was shown to be a potent inhibitor of the VirA-VirG two-component system which mediates host recognition and activates virulence gene transcription in the soil pathogen Agrobacterium tumefaciens. The hydrolytic lability of HDMBOA creates a steady-state zone of inhibition circumscribing the young maize seedling. We now show that rather than the HDMBOA natural product, an o-imidoquinone decomposition intermediate, (3Z)-2,2-dihydroxy-N-(4-methoxy-6-oxocyclohexa-2,4-dienylidene)acetamide, can function as an inhibitor of virulence gene expression in A. tumefaciens. Structural characterization of this o-imidoquinone intermediate clarifies several issues related to the decomposition pathways available to this class of antibiotics. Of direct ecological importance, this species is produced rapidly and quantitatively within the more neutral pH ranges of the A. tumefaciens cytoplasm, while HDMBOA is more persistent at the slightly acidic pH common to many soils. These results suggest the rather intriguing possibility that the physical instability of the benzoxazinone antibiotics may not only create a steady-state local defense, but also enable a "pro-drug" strategy directed against bacterial environmental sensing.
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U2 - 10.1021/cb600051w
DO - 10.1021/cb600051w
M3 - Article
C2 - 17163664
AN - SCOPUS:34249282652
SN - 1554-8929
VL - 1
SP - 165
EP - 175
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 3
ER -