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The Journal of Antibiotics Oct 1999From a rare actinomycete strain #8 isolated from soil as arbekacin (ABK) resistant, we cloned a gene segment (0.9 kb) conferring multiple resistance to aminoglycoside... (Comparative Study)
Comparative Study
Role of aminoglycoside 6'-acetyltransferase in a novel multiple aminoglycoside resistance of an actinomycete strain #8: inactivation of aminoglycosides with 6'-amino group except arbekacin and neomycin.
From a rare actinomycete strain #8 isolated from soil as arbekacin (ABK) resistant, we cloned a gene segment (0.9 kb) conferring multiple resistance to aminoglycoside (AG) antibiotics with 6'-NH2 including semisynthetic ones except ABK and neomycin (NM). Enzymatic modification using cell free extracts from Streptomyces lividans TK21/pANT-S2 carrying the cloned gene revealed that the gene coded for an AG 6'-acetyltransferase [AAC(6')] capable of acetylating all of the tested AGs with 6'-NH2 including semisynthetic ones and astromicin. The substrate specificity of the enzyme was thus similar to that of AAC(6')-Ie of Enterococcus faecalis. Antibiotic assay revealed a weak but clear antibiotic activity of 6'-N-acetylABK (8% of ABK activity) in contrast with substantial inactivation by the AAC(6') of the other AGs including amikacin and isepamicin. The NM acetylation by the AAC(6') also did not result in NM inactivation. It seems thus likely that AAC(6')-dependent resistance to ABK and NM, if it emerges, will remain at low level.
Topics: Acetylation; Acetyltransferases; Actinomycetales; Aminoglycosides; Anti-Bacterial Agents; Cloning, Molecular; Dibekacin; Drug Resistance, Multiple; Neomycin; Streptomyces; Structure-Activity Relationship
PubMed: 10604758
DOI: 10.7164/antibiotics.52.889 -
The Tohoku Journal of Experimental... Sep 1998Four arbekacin (ABK)-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were studied regarding their mechanism of...
Four arbekacin (ABK)-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were studied regarding their mechanism of aminoglycoside-resistance. Metabolites of amikacin (AMK) and gentamicin(GM) were obtained by reaction with excess amounts of crude enzyme preparation extracted from the ABK-resistant MRSA strains. Then the metabolites were then isolated and analyzed by means of 1H, 13C-nuclear magnetic resonance. The AMK-modification was 4'''-N-acetylation. However, the site of GM-acetylation may be 6'-N-position by these strains.
Topics: Acetylation; Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Microbial; Methicillin; Methicillin Resistance; Penicillins; Staphylococcus aureus
PubMed: 9915109
DOI: 10.1620/tjem.186.67 -
The Journal of Antibiotics Aug 1998Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X, derived from... (Comparative Study)
Comparative Study
Kanamycin group antibiotics were subjected to enzymatic acetylation by a cell free extract containing an aminoglycoside 3-N-acetyltransferase, AAC(3)-X, derived from Streptomyces griseus SS-1198PR. Characterization of the incubated reaction mixtures by TLC and antibiotic assay revealed that a product retaining activity was specifically formed from arbekacin, an anti-MRSA semisynthetic aminoglycoside. The structural determination demonstrated that acetylation occurred at the 3"-amino group in arbekacin and amikacin, and at the 3-amino group in dibekacin as in the case of kanamycin. These results should reflected the effect of the (S)-4-amino-2-hydroxybutyryl side chain which is present in arbekacin and amikacin, but absent in dibekacin and kanamycin. The 3"-N-acetylation is the first finding in the enzymatic modifications of aminoglycoside antibiotics. 3"-N-Acetylarbekacin showed antibiotic activity as high as that of 2'-N-acetylarbekacin reported previously, whereas 3"-N-acetylamikacin showed no substantial activity. Thus, our results illuminated a novel aspect of arbekacin distinct from the other aminoglycosides.
Topics: Acetylation; Acetyltransferases; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Microbial Sensitivity Tests; Molecular Structure
PubMed: 9766465
DOI: 10.7164/antibiotics.51.735 -
Antimicrobial Agents and Chemotherapy Oct 1996A novel gene encoding an aminoglycoside 2'-N-acetyltransferase (AAC) was cloned from Mycobacterium fortuitum. DNA sequencing results identified an open reading frame...
A novel gene encoding an aminoglycoside 2'-N-acetyltransferase (AAC) was cloned from Mycobacterium fortuitum. DNA sequencing results identified an open reading frame that we have called aac(2')-Ib encoding a putative protein with a predicted molecular mass of 24,800 Da. The deduced AAC(2')-Ib protein showed homology to the AAC(2')-Ia from Providencia stuartii. This is the second member of a subfamily of AAC(2')-I enzymes to be identified. No homology was found with other acetyltransferases, including all of the AAC(3) and AAC(6') proteins. The aac(2')-Ib gene cloned in a mycobacterial plasmid and introduced in Mycobacterium smegmatis conferred resistance to gentamicin, tobramycin, dibekacin, netilmicin, and 6'-N-ethylnetilmicin. DNA hybridization with an intragenic probe of aac(2')-Ib showed that this gene was present in all 34 strains of M. fortuitum tested. The universal presence of the aac(2')-Ib gene in M. fortuitum was not correlated with any aminoglycoside resistance phenotype, suggesting that this gene may play a role in the secondary metabolism of the bacterium.
Topics: Acetyltransferases; Amino Acid Sequence; Aminoglycosides; Anti-Bacterial Agents; Base Sequence; Chromosomes, Bacterial; DNA, Bacterial; Drug Resistance, Microbial; Escherichia coli; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Mycobacterium; Nucleic Acid Hybridization; Plasmids; Providencia
PubMed: 8891143
DOI: 10.1128/AAC.40.10.2350 -
The Journal of Antibiotics May 1996Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside... (Comparative Study)
Comparative Study
Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.
Topics: Acetylation; Acetyltransferases; Acylation; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Microbial Sensitivity Tests; Molecular Structure; Streptomyces; Structure-Activity Relationship
PubMed: 8682723
DOI: 10.7164/antibiotics.49.458 -
The Journal of Antibiotics Jul 1994Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino...
Based on our studies on the enzymatic modifications of arbekacin by methicillin-resistant Staphylococcus aureus (MRSA), replacement of the 2''-hydroxyl group by an amino group in arbekacin was designed to synthesize derivatives that would be active against MRSA. 2''-Amino-2''-deoxyarbekacin and five analogs were synthesized starting from dibekacin. Among them, 2''-amino-2''-deoxyarbekacin and the 5-epiamino analog showed excellent antibacterial activities against not only MRSA but also Gram-negative bacteria including Pseudomonas, and lower toxicities than arbekacin.
Topics: Carbohydrate Sequence; Dibekacin; Gram-Negative Bacteria; Magnetic Resonance Spectroscopy; Methicillin Resistance; Microbial Sensitivity Tests; Molecular Sequence Data; Staphylococcus; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 8071128
DOI: 10.7164/antibiotics.47.821 -
The Journal of Antibiotics Apr 1994
Comparative Study
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus
PubMed: 8195054
DOI: 10.7164/antibiotics.47.507 -
Hinyokika Kiyo. Acta Urologica Japonica Dec 1993We experienced 20 cases of methicillin-resistant Staphylococcus aureus (MRSA) infection from April 1991 to September 1992. Of them, 9 showed substantial morbidity and...
We experienced 20 cases of methicillin-resistant Staphylococcus aureus (MRSA) infection from April 1991 to September 1992. Of them, 9 showed substantial morbidity and their clinical courses are herein reported. The clinical presentations of these cases were wound infection and enterocolitis. Although in 8 cases MRSA was eradicated in 14 to 160 days by effective antibiotics administration, one had a fatal outcome. All strains isolated showed similar drug-sensitivity pattern suggesting hospital infection. Sensitivity to vancomycin and arbekacin, however, remained high and these drugs were effective clinically. It should be stressed that treatment strategy of MRSA infection should consist of isolation of patients with MRSA from other patients, use of disposable equipment and products, and serious and continuing concerns of medical personal on communicability of MRSA.
Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Enterocolitis; Female; Humans; Immunocompromised Host; Male; Methicillin Resistance; Middle Aged; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus; Urinary Bladder Neoplasms; Vancomycin
PubMed: 8285164
DOI: No ID Found -
Nihon Hinyokika Gakkai Zasshi. the... Mar 1993Out of 110 strains of Staphylococcus aureus isolated from 1985 to 1990, isolation rate of methicillin-resistant S. aureus (MRSA) was investigated. Nineteen strains of 59...
Out of 110 strains of Staphylococcus aureus isolated from 1985 to 1990, isolation rate of methicillin-resistant S. aureus (MRSA) was investigated. Nineteen strains of 59 S. aureus from outpatients and 20 strains of 51 S. aureus from inpatients were determined as MRSA. Isolation frequency of MRSA from inpatients was increasing in the recent two years. Coagulase type, enterotoxin type and production of toxic shock syndrome toxin-1 (TSST-1) were examined in 22 strains of MRSA. Coagulase type II (86%), enterotoxin type C (68%) and TSST-1 positive strain was most dominant. Susceptibility of MRSA to 4 antimicrobial agents were measured, MRSA were sensitive to vancomycin (VCM), arbekacin (ABK) and minocycline, but resistant to flomoxef. Thirty-four patients from whom MRSA was isolated including 20 patients from urine, 13 from pus and 1 from blood, were analyzed clinically. Pyuria was not recognized in some cases in whom MRSA was isolated from their urine. Concomitant polymicrobial infection was frequently noted in those patients with MRSA in their urinary tract. These facts show that the pathogenic role of MRSA in the urinary tract infection was not significant. On the other hand, when MRSA was isolated from pus or blood, serious infections could be caused by MRSA, especially in compromised host. Regarding the treatment in these cases, administration of VCM or ABK was though to be necessary.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cephalosporins; Dibekacin; Humans; Immunocompromised Host; Methicillin Resistance; Minocycline; Serotyping; Staphylococcus aureus; Urologic Diseases; Vancomycin
PubMed: 8515639
DOI: 10.5980/jpnjurol1989.84.514 -
The Journal of Antibiotics Mar 1993
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 8478274
DOI: 10.7164/antibiotics.46.531