title: Investigations into the in vitro antimicrobial activity and mode of action of the phenazine antibiotic D-alanylgriseoluteic acid.
abstract: D-Alanylgriseoluteic acid (AGA) is a potent antimicrobial phenazine compound produced by Pantoea agglomerans (Erwinia herbicola) Eh1087. Susceptibility tests against a range of microbes indicated that AGA had a broad spectrum of antimicrobial activity and was particularly active against Gram-positive pathogens. Comparison of the in vitro efficacy of AGA with eight other antibiotics against 119 clinical isolates of Streptococcus pneumoniae demonstrated that all were inhibited by low concentrations of AGA (minimal inhibitory concentration range <or=0.06-0.75 microg/mL), regardless of their susceptibility to other antimicrobials. Investigations into the mode of action of AGA revealed that it induced the SOS response in Escherichia coli and slightly increased the frequency of GC-AT transition mutations. In cell-free assays, both AGA and griseoluteic acid reduced cytochrome c in the presence of a redox recycler (ferredoxin-NADP(+) reductase), but AGA was six to seven times more readily reduced than griseoluteic acid in the absence of the reductase. The potency and broad spectrum of AGA activity suggest that AGA may warrant further investigation.
authors.affiliation: Department of Plants Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. stephen.giddens@plants.ox.ac.uk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Giddens
authors.forename: David C
authors.initials: DC
authors.lastname: Bean
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010619:Phenazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013014:SOS Response, Genetics / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D009153:Mutagens; D016877:Oxidants; D010619:Phenazines; C518060:alanylgriseoluteic acid; D045304:Cytochromes c; D005287:Ferredoxin-NADP Reductase; D000409:Alanine