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Antimicrobial Agents and Chemotherapy, October 1998, p. 2612-2619, Vol. 42, No. 10
Institut de Génétique et
Microbiologie, UMR 2225, Université Paris-Sud XI, Orsay, France
Received 11 March 1998/Returned for modification 15 May
1998/Accepted 4 August 1998
In Streptomyces ambofaciens, the producer of the
macrolide antibiotic spiramycin, an open reading frame (ORF) was found
downstream of srmA, a gene conferring resistance to
spiramycin. The deduced product of this ORF had high degrees of
similarity to Streptomyces lividans glycosyl transferase,
which inactivates macrolides, and this ORF was called gimA.
The cloned gimA gene was expressed in a susceptible host
mutant of S. lividans devoid of any
background macrolide-inactivating glycosyl transferase activity. In the
presence of UDP-glucose, cell extracts from this strain could
inactivate various macrolides by glycosylation. Spiramycin was not
inactivated but forocidin, a spiramycin precursor, was modified. In
vivo studies showed that gimA could confer low levels of
resistance to some macrolides. The spectrum of this resistance differs
from the one conferred by a rRNA monomethylase, such as SrmA. In
S. ambofaciens, gimA was inactivated by
gene replacement, without any deleterious effect on the survival of the
strain, even under spiramycin-producing conditions. But the
overexpression of gimA led to a marked decrease in
spiramycin production. Studies with extracts from wild-type and gimA-null mutant strains revealed the existence of
another macrolide-inactivating glycosyl transferase activity with a
different substrate specificity. This activity might compensate for the effect of gimA inactivation.
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Characterization of a Glycosyl Transferase Inactivating
Macrolides, Encoded by gimA from Streptomyces
ambofaciens
*
Corresponding author. Mailing address: Laboratoire de
Biologie et Génétique Moléculaire, Institut de
Génétique et Microbiologie, Bât. 400, Université Paris-Sud XI, 91405 Orsay Cedex, France. Phone: 33 (0)
1 69 15 69 13. Fax: 33 (0) 1 69 15 72 96. E-mail: pernodet{at}igmors.u-psud.fr.
Antimicrobial Agents and Chemotherapy, October 1998, p. 2612-2619, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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