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Biomedical subjects

A Sunada

Publications and source records attributed to A Sunada.

12 recordsLinked to original sources
PubMed2003

In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.

We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.

Anti-Bacterial Agents↗
PubMed2001

Utility of Etest in choosing appropriate agents to treat fungal keratitis.

PURPOSE: To evaluate the utility of Etest in choosing the appropriate treatment of fungal keratitis. METHODS: Etest was used to determine the drug sensitivities of isolates from the eyes of three patients with fungal keratitis, and the clinical outcomes of treatment with selected drugs were evaluated. RESULTS: In all cases, drug sensitivity demonstrated by Etest accorded with clinical efficacy of the drugs. CONCLUSION: The results in these cases suggest that evaluating drug sensitivities with Etest is an efficient means of selecting optimal pharmacotherapy for fungal keratitis.

Aged↗
PubMed2000

Identification and characterization of the point mutation which affects the transcription level of the chromosomal 3-N-acetyltransferase gene of Streptomyces griseus SS-1198.

We determined the molecular basis for the enhanced expression of the aac(3)-Xa gene encoding an aminoglycoside 3-N-acetyltransferase in Streptomyces griseus. A C-->T substitution was identified at the putative promoter of the mutant gene. RNA analyses demonstrated that the substitution caused a marked increase in the production of the gene-specific transcripts. Therefore, it seemed very likely that the aac(3)-Xa gene was activated by the substitution resulting in the emergence of a stronger promoter.

Arylamine N-Acetyltransferase↗
PubMed2000

Double stage activity in aminoglycoside antibiotics.

Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKB also retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM, paromomycin], NM retained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTM and istamycin B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others. Streptomyces lividans TK21 containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.

Acetylation↗
PubMed1999

Enzymatic 1-N-acetylation of paromomycin by an actinomycete strain #8 with multiple aminoglycoside resistance and paromomycin sensitivity.

An actinomycete strain #8 with multiple aminoglycoside (AG) resistance and paromomycin (PRM) sensitivity was examined for its capability of enzymatic modification of AGs. Cell free extracts from the strain converted all of the examined AGs including PRM in the presence of acetyl CoA. PRM was completely modified to at least two products (major and minor spots upon TLC) without significant reduction of the antibiotic activity of the reaction mixture. The structure determination and antibiotic assay of the purified major product revealed l-N-acetylPRM and its antibiotic activity (12% activity of PRM), indicating the existence of AAC(1). It was thus obvious that the 1-N-acetylation of PRM did not cause PRM resistance. Apramycin, the substrate of the known AAC(1), was not readily acetylated, suggesting that the AAC(1) of strain #8 is a new type. Two diacetylated products (1,2'-di-N-acetylPRM and 1,6"'-di-N-acetylPRM) were found in the minor spot, suggesting the existence of additional AACs.

Acetylation↗
PubMed1999

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.

Acetylation↗
PubMed1998

The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity.

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.

Acetylation↗
PubMed1996

Enzymatic 2'-N-acetylation of arbekacin and antibiotic activity of its product.

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.

Acetylation↗