Mechanism of multiple aminoglycoside resistance of kasugamycin-producing Streptomyces kasugaensis MB273: involvement of two types of acetyltransferases in resistance to astromicin group antibiotics.
The biochemical basis for the multiple resistance to aminoglycoside antibiotics (AGs) of kasugamycin-producing Streptomyces kasugaensis MB273 was studied. The strain was resistant to a wide range of deoxystreptamine (DOS)-containing AGs as well as astromicin (ASTM) group antibiotics. These AGs strongly inhibited in vitro polyU-directed polyphenylalanine-synthesis using ribosomes from the strain, while they were acetylated and inactivated by the MB273 cell free extract supplemented with acetyl-CoA. It seemed thus likely that the acetyltransferase activity played a critical role for the multiple AG resistance. The acetylation was selective to AGs with 2'-NH2, suggesting the involvement of aminoglycoside 2'-N-acetyltransferase, AAC (2'). Interestingly, the acetylation of istamycin B (ISM-B; an ASTM group AG) resulted in the formation of two different products (1-N-acetyl ISM-B and 2"-N-acetyl ISM-B) at a similar ratio. In this context, an AAC (2') gene cloned as an ISM-B resistance gene from the strain MB273 directed the conversion of ISM-B to only 1-N-acetyl ISM-B. It seemed likely that two types of AACs [AAC(2') and a novel one] were involved in the mechanism of resistance to ASTM group AGs.
Hotta
K
K
National Institute of Health, Tokyo, Japan.
Ogata
T
T
Ishikawa
J
J
Okanishi
M
M
Mizuno
S
S
Morioka
M
M
Naganawa
H
H
Okami
Y
Y
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000502:physiology; D015394:Molecular Structure; D013302:Streptomyces / Q000187:drug effects* / Q000378:metabolism*
C101447:1-N-acetylistamycin B; C101448:2''-N-acetylistamycin B; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C022949:istamycins; C023384:fortimicin A; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; C100305:kasugamycin