• 제목/요약/키워드: Aminoglycoside antibiotics

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Resistance of Kanamycin- and Neomycin-Producing Streptomycetes to Aminoglycoside Antibiotics

  • Goo, Yang-Mo;Choi, Seok-Rye;Kim, Kyung-Ja
    • Bulletin of the Korean Chemical Society
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    • v.15 no.7
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    • pp.568-571
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    • 1994
  • Streptmyces fradiae NRRL B1195 and Streptomyces kanamyceticus IFO 13414 are highly resistant to the antibiotics they produce. The ribosomes of these organisms are found to be susceptible to the antibiotics, but the cell free extract of S fradiae is found to contain a phosphotransferase and an acetyltransferase which inactivate kanamycin and neomycin, and that of S. kanamyceticus an acetyltransferse which inactivates kanamycin and neomycin. The resistance of these organisms against streptomycin is found to be due to the resistant ribosomes; actually streptomycin activates their ribosomal systems for the synthesis of polyphenylalanine.

Isolation, structure elucidation and physicochemical properties of novel antibiotic polypeptide, $\varepsilon-(L-\beta-Iysine)$ polypeptide from Streptomyces sp. DWGS2

  • Donghyuk Shin;Kim, Daesung;Lee, Deoggeun;Lee, Hyeongkyu;Hoshik Won
    • Journal of the Korean Magnetic Resonance Society
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    • v.6 no.1
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    • pp.69-77
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    • 2002
  • During the screening of material which has the antimicrobial activity against aminoglycoside-resistant bacteria, A new material $\varepsilon$-(L-$\beta$-Iysine) polypeptide from a culture medium of Streptomyces sp.(DWGS2) was isolated, and the structure and the physicochemical properties of the new material were elucidated. The new material was separated by column chromatography of the culture medium using Dowex1$\times$2, Silica gel, and Sephadex LH20 etc. The chemical structure and molecular weight were determined with the data of various NMR experiments, MALDI mass, and ESI mass experiments. The antimicrobial activity of $\varepsilon$-(L-$\beta$-Iysine) polypeptide is not only better than equal to the activity of known aminoglycoside type of antibiotics(MIC=3.125 - 6.25ug/mL) but also effective against aminoglycoside-resistant bacteria and fungi. If the mechanism of antimicrobial activity against aminoglycoside- resistant bacteria is figured out, the $\varepsilon$-(L-$\beta$-Iysine) polypeptide can be utilized for the treatment of diseases caused by aminoglycoside-resistant bacteria.

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Studies of the Physiological Activity of Korean Ginseng (Part 2) The effects of Ginseng Saponin on the Antimicrobial Activity of Antibiotics (인삼의 생리활성에 관한 연구 (제 2 보)항생물질의 항균활성에 미치는 인삼 Saponin의 영향)

  • 전홍기;김선희
    • Microbiology and Biotechnology Letters
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    • v.10 no.3
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    • pp.163-169
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    • 1982
  • The possible effects in vivo on the duel usage of sinseng saponin and antibiotics were studied in vitro with microorganisms. Streptomycin.sulfate, kanamycin.sulfate and gentamycin.sulfate as being an aminoglycoside-antibiotic substance showed a general synergism by the interaction of ginseng saponin and these antibiotics. But kanamycin.sulfate and gentamycin.sulfate did not show a synergism in their original antimicrobial activity against Er-winia aroideoe. Chloramphenicol as being a benzene derivative displayed an increased antimicrobial activity by the interactions of ginseng saponin and this antibiotic against Salmonella typhi, Aerobacter aerogenes and the genus Serrotia. This antibiotic also showed the decreased antimicrobial activity against Bacillus subtilis, Bacillus megaterium and Escherichia coli, but did not show an uniform antimicrobial activity against others.

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Heterologous Production and Detection of Recombinant Directing 2-Deoxystreptamine (DOS) in the Non-Aminoglycoside-Producing Host Streptomyces venezuelae YJ003

  • Kurumbang, Nagendra Prasad;Oh, Tae-Jin;Liou, Kwangkyoung;Sohng, Jae-Kyung
    • Journal of Microbiology and Biotechnology
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    • v.18 no.5
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    • pp.866-873
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    • 2008
  • 2-Deoxystreptamine is a core aglycon that is vital to backbone formation in various aminoglycosides. This core structure can be modified to develop hybrid types of aminoglycoside antibiotics. We obtained three genes responsible for 2-deoxystreptamine production, neo7, neo6, and neo5, which encode 2-deoxy-scyllo-inosose synthase, L-glutamine: 2-deoxy-scyllo-inosose aminotransferase, and dehydrogenase, respectively, from the neomycin gene cluster. These genes were cloned into pIBR25, a Streptomyces expression vector, resulting in pNDOS. The recombinant pNDOS was transformed into a non-aminoglycoside-producing host, Streptomyces venezuelae YJ003, for heterologous expression. Based on comparisons of the retention time on LC-ESI/MS and ESI-MS data with those of the 2-deoxystreptamine standard, a compound produced by S. venezuelae YJ003/pNDOS was found to be 2-deoxystreptamine.

Effect of Gentamicin on Sodium Transport in Human Erythrocytes (Gentamicin이 적혈구막을 통한 $Na^+$ 이동에 미치는 영향)

  • Kim, Kyung-Hyo;Park, Kae-Sook;Kim, Hee-Jin;Shin, Ho-Im;An, Mi-Ra;Kang, Bok-Soon
    • The Korean Journal of Physiology
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    • v.23 no.1
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    • pp.23-34
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    • 1989
  • Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.

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Mechanism of Action of and Resistance to Aminoglycoside Antibiotics

  • Tanaka, Nobuo
    • Archives of Pharmacal Research
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    • v.6 no.1
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    • pp.93-102
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    • 1983
  • Waksman's group discovered SM in 1944, and opened a new field of antibiotcs: i. e. AGs. A large group of antibiotics containing aminosugar and/or aminocyclitol is called the AGs. A majority of AGs are produced by actinomycetes. In the first period, AGs effective against tuberculosis were chiefly examined. Following the studies on NM and KM, AGs active against staphyllococci and gram-negative robs were investigated. The discovery of GM and synthesis of DKB and AMK led to the studies on the third generation AGs, which show a broad antimicrobial spectrum including Pseudomonas aeruginosa and drug-resistant bacteria. Since opportunistic infection caused by drug-resistant bacteria are increasing, the third generation AGs are extensively investigated at present.

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Analysis and Monitoring of Residues of Aminoglycoside Antibiotics in Livestock Products (축산식품 중 아미노글리코사이드계 항생제 잔류량 분석 및 실태조사)

  • Kang, Young-Woon;Joo, Hyun-Jin;Kim, Yang-Sun;Cho, Yu-Jin;Kim, Hee-Yun;Lee, Gwang-Ho;Kim, Mee-Hye
    • Korean Journal of Food Science and Technology
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    • v.43 no.1
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    • pp.1-5
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    • 2011
  • It is possible that veterinary medicines remain in livestock food products, according to the use of many and various veterinary medicines to protect against disease when livestock animals are breed in limited space. Concentrated and continuous monitoring of residues is needed due to increases in resistance to antibiotics and side effects by eating livestock food products. We developed an analysis method for detecting streptomycin, dihydrostreptomycin, neomycin, gentamicin and spectinomycin in meat using LC/MS/MS and measured sensitivity, precision, accuracy, linearity and recovery according to CODEX guidelines to acquire confidence in the analysis method. Based on the results, we acquired good sensitivity compared to the maximum residue limit (MRL) as limits of detection (LOD) were 0.002-0.016 mg/kg and limits of quantification (LOQ) were 0.006-0.050 mg/kg. The analysis method satisfied the CODEX guidelines. The linearity ($r^2$) values of aminoglycoside antibiotics were 0.9936-0.9980, recoveries were 60-110% and relative standard deviations (RSD) were within 15%. As a result of monitoring for residues in a total 250 samples of livestock foods such as pork, chicken, and beef by the confirmed method, dihydrostreptomycin and gentamicin were detected in 5 pork samples. The residues of these antibiotics were within the MRLs. Thus, the detection ratio was 2% as 5 samples were identified from 250 samples.

Differential analysis of amikacin and butirosin

  • Nam, Doo-Hyun;Ryu, D.Y.
    • Archives of Pharmacal Research
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    • v.5 no.2
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    • pp.87-91
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    • 1982
  • In order to develop an analytical method for amikacin and butirosin in presence of their parent antibiotics, kanamycin A and ribostamycin, high-performance liquid chromatographic technique and microbioassay method were evaluated and compared. Using high performance liquid chromatography, two acylated antibiotics, amikacin and butirosin was partially separated from their parent antibiotics, to provide a qualitative analytical method. In microbioassay using Pseudomonas aeruginosa TI-13, a producer of aminoglycoside-3-phosphotransferase I, only acylated antibiotics were selectively analyzed when paper disc-susceptibility assay was used. The standard curve showed a good correlation between the response and odse in semilogarithmic plat with correlation coefficients above 0.96, and analytical deviation from expected dose was within 10%.

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In Vivo Characterization of Phosphotransferase-Encoding Genes istP and forP as Interchangeable Launchers of the C3',4'-Dideoxygenation Biosynthetic Pathway of 1,4-Diaminocyclitol Antibiotics

  • Nguyen, Lan Huong;Lee, Na Joon;Hwang, Hyun Ha;Son, Hye Bin;Kim, Hye Ji;Seo, Eun Gyo;Nguyen, Huu Hoang;Park, Je Won
    • Journal of Microbiology and Biotechnology
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    • v.29 no.3
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    • pp.367-372
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    • 2019
  • Deactivation of aminoglycosides by their modifying enzymes, including a number of aminoglycoside O-phosphotransferases, is the most ubiquitous resistance mechanism in aminoglycoside-resistant pathogens. Nonetheless, in a couple of biosynthetic pathways for gentamicins, fortimicins, and istamycins, phosphorylation of aminoglycosides seems to be a unique and initial step for the creation of a natural defensive structural feature such as a 3',4'-dideoxy scaffold. Our aim was to elucidate the biochemical details on the beginning of these C3',4'-dideoxygenation biosynthetic steps for aminoglycosides. The biosynthesis of istamycins must surely involve these 3',4'-didehydroxylation steps, but much less has been reported in terms of characterization of istamycin biosynthetic genes, especially about the phosphotransferase-encoding gene. In the disruption and complementation experiments pointing to a putative gene, istP, in the genome of wild-type Streptomyces tenjimariensis, the function of the istP gene was proved here to be a phosphotransferase. Next, an in-frame deletion of a known phosphotransferase-encoding gene forP from the genome of wild-type Micromonospora olivasterospora resulted in the appearance of a hitherto unidentified fortimicin shunt product, namely 3-O-methyl-FOR-KK1, whereas complementation of forP restored the natural fortimicin metabolite profiles. The bilateral complementation of an istP gene (or forP) in the ${\Delta}forP$ mutant (or ${\Delta}istP$ mutant strain) successfully restored the biosynthesis of 3',4'-dideoxy fortimicins and istamycins, thus clearly indicating that they are interchangeable launchers of the biosynthesis of 3',4'-dideoxy types of 1,4-diaminocyclitol antibiotics.

NaCl Concentration-Dependent Aminoglycoside Resistance of Halomonas socia CKY01 and Identification of Related Genes

  • Park, Ye-Lim;Choi, Tae-Rim;Kim, Hyun Joong;Song, Hun-Suk;Lee, Hye Soo;Park, Sol Lee;Lee, Sun Mi;Kim, Sang Hyun;Park, Serom;Bhatia, Shashi Kant;Gurav, Ranjit;Sung, Changmin;Seo, Seung-Oh;Yang, Yung-Hun
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.250-258
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    • 2021
  • Among various species of marine bacteria, those belonging to the genus Halomonas have several promising applications and have been studied well. However, not much information has been available on their antibiotic resistance. In our efforts to learn about the antibiotic resistance of strain Halomonas socia CKY01, which showed production of various hydrolases and growth promotion by osmolytes in previous study, we found that it exhibited resistance to multiple antibiotics including kanamycin, ampicillin, oxacillin, carbenicillin, gentamicin, apramycin, tetracycline, and spectinomycin. However, the H. socia CKY01 resistance pattern to kanamycin, gentamicin, apramycin, tetracycline, and spectinomycin differed in the presence of 10% NaCl and 1% NaCl in the culture medium. To determine the mechanism underlying this NaCl concentration-dependent antibiotic resistance, we compared four aminoglycoside resistance genes under different salt conditions while also performing time-dependent reverse transcription PCR. We found that the aph2 gene encoding aminoglycoside phosphotransferase showed increased expression under the 10% rather than 1% NaCl conditions. When these genes were overexpressed in an Escherichia coli strain, pETDuet-1::aph2 showed a smaller inhibition zone in the presence of kanamycin, gentamicin, and apramycin than the respective control, suggesting aph2 was involved in aminoglycoside resistance. Our results demonstrated a more direct link between NaCl and aminoglycoside resistance exhibited by the H. socia CKY01 strain.