STREPTOMYCES-ANTIBIOTICUS CONTAINS AT LEAST 3 OLEANDOMYCIN-RESISTANCEDETERMINANTS, ONE OF WHICH SHOWS SIMILARITY WITH PROTEINS OF THE ABC-TRANSPORTER SUPERFAMILY
Am. Rodriguez et al., STREPTOMYCES-ANTIBIOTICUS CONTAINS AT LEAST 3 OLEANDOMYCIN-RESISTANCEDETERMINANTS, ONE OF WHICH SHOWS SIMILARITY WITH PROTEINS OF THE ABC-TRANSPORTER SUPERFAMILY, Molecular microbiology, 8(3), 1993, pp. 571-582
Three different DNA fragments of an oleandomycin producer, Streptomyce
s antibioticus, conferring oleandomycin resistance were cloned in plas
mid pIJ702 and expressed in Streptomyces lividans and in Streptomyces
albus. These oleandomycin resistance determinants were designated as o
leA (pOR400), oleB (pOR501) and oleC (pOR800). oleA and oleC are close
ly linked in the chromosome as they were both obtained together in two
cosmid clones that were isolated from a genomic library. Sequencing o
f the oleC resistance determinant revealed four complete open reading
frames (ORFs) and the C-terminal end of a fifth. The functions of orf1
and orf2 are unknown since they did not show significant similarity w
ith other sequences in the data bases. The orf3 gene product has simil
arity with some proteins involved in iron and vitamin B12 uptake In ba
cteria. The orf4 gene product had a hydrophilic profile and showed imp
ortant similarity with proteins containing typical ATP-binding domains
characteristic of the ABC-transporter superfamily and involved in mem
brane transport and, particularly, with several genes conferring resis
tance to various macrolide antibiotics and anticancer drugs. The last
gene, orf5, is translationally coupled to orf4 and codes for a hydroph
obic polypeptide containing several transmembrane domains characterist
ic of integral membrane proteins. Subcloning and deletion experiments
limited the resistance determinant to a 0.9 kb PstI-SphI fragment and
only orf4 is included in this fragment. These results suggest that res
istance to oleandomycin conferred by oleC (orf4) is probably due to an
efflux transport system of the ABC-transporter superfamily.