Intracellular glycosylation and active efflux as mechanisms for resistance to oleandomycin in Streptomyces antibioticus, the producer organism.
Resistance to macrolides in producing organisms can be achieved by target site modification, intracellular inactivation of the antibiotic or active efflux mechanisms for the excretion of the antibiotic. The oleandomycin producer, Streptomyces antibioticus, possesses oleandomycin-sensitive ribosomes all along the cell cycle. However, it contains an intracellular glycosyltransferase capable of inactivating oleandomycin in the presence of UDP-glucose as cofactor. The correspondent gene (oleD) has been cloned and sequenced and the glycosyltransferase purified. Two other genes (oleB and oleC) that confer oleandomycin resistance have been cloned and characterized and both encode ABC (ATP-Binding Cassette) transporters. These may constitute the excretion mechanism throughout which the glycosylated oleandomycin is excreted. A second enzyme activity has been purified from culture supernatants of the oleandomycin producer that releases the glucose from the inactive glycosylated oleandomycin generating active antibiotic. This enzyme would probably catalyse the last step in the biosynthesis of oleandomycin.
Salas
J A
JA
Departamento de Biología Funcional, Universidad de Oviedo.
Hernández
C
C
Méndez
C
C
Olano
C
C
Quirós
L M
LM
Rodríguez
A M
AM
Vilches
C
C
D000595:Amino Acid Sequence; D001693:Biological Transport, Active; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial / Q000235:genetics*; D006031:Glycosylation; D008745:Methylation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009827:Oleandomycin / Q000096:biosynthesis / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000235:genetics; D013303:Streptomyces antibioticus / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
D012335:RNA, Ribosomal; D009827:Oleandomycin