Abstract
During the early 1950s when strongly resistant organisms had not yet appeared, the chemotherapy of most bacterial infections was assumed to be possible. However, tubercle bacilli soon became resistant to streptomycin and new active agents were required for the treatment of tuberculosis. At that time, Umezawa discovered the aminoglycoside antibiotic, kanamycin, in the search for new water-soluble basic antibiotics (H. Umezawa et al. 1957). Kanamycin was evaluated as an effective agent for the treatment of infections with resistant staphylococci and streptomycin-resistant tuberculosis, and later for the treatment of infections with resistant gram-negative bacteria. However, after widespread use of the antibiotic, in 1965 kanamycin-resistant strains appeared in patients, although at a frequency of less than 5%. Therefore, Umezawa undertook studies on the biochemical mechanisms of resistance to aminoglycoside antibiotics (H. Umezawa et al. 1967 a, b). The results of these studies suggested structures which would be active against resistant strains and many derivatives of aminoglycoside antibiotics were synthesized. Among these, 3’,4’-dideoxykanamycin B (dibekacin) (H. Umezawa et al. 1971) was useful in the treatment of infections with resistant gram-positive and -negative bacteria, including pseudomonas, and was marketed in 1975.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abe Y, Nakagawa S, Fujisawa K, Naito T, Kawaguchi H (1977) Aminoglycoside antibiotics. XI. Synthesis and activity of 4’-deoxykanamycin B. J Antibiot (Tokyo) 30:1004–1007
Akiba T, Koyama K, Isshiki Y, Kimura S, Fukushima T (1960) On the mechanism of the development of multiple drug resistance clones of Shigella (in Japanese). Nippon Iji Shimpo 1866:46–50
Benveniste R, Davies J (1971a) R-factor mediated gentamicin resistance: a new enzyme which modifies aminoglycoside antibiotics. FEBS Lett 14:293–296
Benveniste R, Davies J (1971b) Enzymatic acetylation of aminoglycoside antibiotics by Escherichia coli carrying an R-factor. Biochemistry 10:1787–1796
Benveniste R, Davies J (1973) Aminoglycoside antibiotic-inactivating enzymes in Actinomy-cetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc Natl Acad Sci USA 70:2276–2280
Benveniste R, Yamada T, Davies J (1970) Enzymatic adenylylation of streptomycin and spectinomycin by R-factor-resistant Escherichia coli. Infect Immun 1:109–119
Brzezinska M, Davies J (1973) Two enzymes which phosphorylate neomycin and kanamy-cin in Escherichia coli strains carrying R factors. Antimicrob Agents Chemother 3:266–269
Brzezinska M, Benveniste R, Davies J, Daniels PJL, Weinstein J (1972) Gentamicin resistance in strains of Pseudomonas aeruginosa mediated by enzymatic N-acetylation of the deoxystreptamine moiety. Biochemistry 11:761–765
Chevereau M, Daniels PJL, Davies J, LeGoffic F (1974) Aminoglycoside resistance in bacteria mediated by gentamicin acetyltransferase II, an enzyme modifying the 2’-amino group of aminoglycoside antibiotics. Biochemistry 13:598–603
Cochran TG, Abraham DJ (1972) Stereochemistry and absolute configuration of the antibiotic spectinomycin: an X-ray diffraction study. J Chem Soc Chem Commun 494–495
Courvalin P, Weisblum B, Davies J (1977) Aminoglycoside-modifying enzyme of an antibiotic-producing bacterium acts as a determinant of antibiotic resistance in Escherichia coli. Proc Natl Acad Sci USA 74:999–1008
Culbertson TP, Watson DR, Haskell TH (1973) 5”-Amino-5”-deoxybutirosin, a new semisynthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 26:790–793
Daniels PJL, Weinstein J, Tkach RW, Morton J (1974a) Gentamicin derivatives modified at the 2”-position. The preparation of 2”-epi-gentamicin C1 and 2”-deoxy gentamicin C2. J Antibiot (Tokyo) 27:150–154
Daniels PJL, Weinstein J, Nagabhushan TL (1974b) The syntheses of l-N-[(S-4-amino-2-hydroxybutyryljgentamicin C1 and l-N-[(S)-3-amino-2-hydroxypropionyl]gentamicin C1. J Antibiot (Tokyo) 27:889–893
Daniels PJL, Cooper AB, McCombie SW, Nagabhushan TL (1979) Some recent advances in the chemistry of antibiotics of the gentamicin series. Jpn J Antibiot 32:S195-S204
Davies J, O’Connor S (1978) Enzymatic modification of aminoglycoside antibiotics: 3-N-acetyltransferase with broad specificity that determines resistance to the novel aminoglycoside apramycin. Antimicrob Agents Chemother 14:69–72
Davies J, Smith DI (1978) Plasmid-determined resistance to antimicrobial agents. Ann Rev Microbiol 32:469–518
Deushi T, Iwasaki A, Kamiya K, Kunieda T, Mizoguchi T, Nakayama M, Itoh H, Mori T, Oda T (1979a) A new broad-spectrum aminoglycoside antibiotic complex, spor-aricin. I. Fermentation, isolation and characterization. J Antiobiot (Tokyo) 32:173–179
Deushi T, Nakayama M, Watanabe I, Mori T, Naganawa H, Umezawa H (1979b) A new broad-spectrum aminoglycoside antibiotic complex, sporaricin. III. The structures of sporaricins A and B. J Antibiot (Tokyo) 32:187–192
Deushi T, Iwasaki A, Kamiya K, Mizoguchi T, Nakayama M, Itoh H, Mori T (1979c) New aminoglycoside antibiotics, sannamycin. J Antibiot (Tokyo) 32:1061–1065
Doi O, Ogura M, Tanaka N, Umezawa H (1968a) Inactivation of kanamycin, neomycin, and streptomycin by enzymes obtained in cells of Pseudomonas aeruginosa. Appl Microbiol 16:1276–1281
Doi O, Miyamoto M, Tanaka N, Umezawa H (1968b) Inactivation and phosphorylation of kanamycin by drug-resistant Staphylococcus aureus. Appl Microbiol 16:1282–1284
Doi O, Kondo S, Tanaka N, Umezawa H (1969) Purification and properties of kanamycin-phosphorylating enzyme from Pseudomonas aeruginosa. J Antibiot (Tokyo) 22:273–282
Egan RS, Stanaszek RS, Cirovic M, Mueller SL, Tadanier J, Martin JR, Collum P, Goldstein AW, Devault RL, Sinclair AC, Fager EE, Mitscher LA (1977) Fortimicins A and B, new aminoglycoside antibiotics. III. Structural identification. J Antibiot (Tokyo) 30:552–563
Fu KP, Neu HC (1978) Activity of 5-episisomicin compared with that of other aminoglycosides. Antimicrob Agents Chemother 14:194–200
Fukasawa K, Sakurai H, Shimizu S, Naganawa H, Kondo S, Kawabe H, Mitsuhashi S (1980) 3”-Phosphoryldihydrostreptomycin produced by the inactivating enzyme of Er-winia carotovora. J Antibiot (Tokyo) 33:122–123
Haas M, Biddlecome S, Davies J, Luce CE, Daniels PJL (1976) Enzymatic modification of aminoglycoside antibiotics: a new 6’-N-acetylating enzyme from Pseudomonas aeruginosa isolate. Antimicrob Agents Chemother 9:945–950
Hanessian S, Yatele J (1980) Aminoglycoside antibiotics. 4’-Deoxyneomycin and 4’-deoxy-paromamine. J Antibiot (Tokyo) 33:675–678
Hanessian S, Massé R, Capmeau M (1977) Aminoglycoside antibiotics: synthesis of 5”-amino-5”-deoxyneomycin and 5”-amino-5”-deoxyparomomycin. J Antibiot (Tokyo) 30:893–896
Hirayama N, Shirahata K, Ohashi Y, Sasada Y, Martin JR (1978) Structure of fortimicin B. Acta Crystallogr Sect B Struct Crystallogr Cryst Chem B34:2648–2650
Hsiang MW, White TJ, Davies JE (1978) NH2-Terminal sequence of the aminoglycoside acetyltransferase (3)-I mediated by plasmid RIP 135. FEBS Lett 92:97–99
Hori M, Umezawa H (1967) Miscoding activities of biologically inactivated kanamycins. J Antiobiot (Tokyo) A20:386–387
Iida T, Sato M, Matsubara I, Mori Y, Shirahata K (1979) The structures of fortimicins C, D, and KE. J Antibiot (Tokyo) 32:1273–1279
Ikeda D, Tsuchiya T, Umezawa S, Umezawa H, Hamada M (1973a) Synthesis of 3’,4’-dideoxybutirosin B. J Antibiot (Tokyo) 26:307–309
Ikeda D, Tsuchiya T, Umezawa S, Umezawa H (1973b) Synthesis of 3’-deoxyribostamycin. J Antibiot (Tokyo) 26:799–801
Ikeda D, Nagaki F, Umezawa S, Tsuchiya T, Umezawa H (1975) Synthesis of 3’-deoxy-butirosin B. J Antibiot (Tokyo) 28:616–618
Ikeda D, Miyasaka T, Yoshida K, Iinuma K, Kondo S, Umezawa H (1979) The chemical conversion of gentamine C1a into gentamine C2 and its 6’-epimer. J Antibiot (Tokyo) 32:1357–1359
Inouye S, Ohba K, Shomura T, Kojima M, Tsuruoka T, Yoshida J, Kato N, Ito M, Amano S, Omoto S, Ezaki N, Ito T, Niida T, Watanabe K (1979) A novel aminoglycoside antibiotic, substance SF-2052. J Antibiot (Tokyo) 32:1354–1356
Kawabe H, Mitsuhashi S (1971) Inactivation of dihydrostreptomycin by Staphylococcus aureus. Jpn J Microbiol 15:545–548
Kawabe H, Kondo S, Umezawa H, Mitsuhashi S (1975) R factor-mediated aminoglycoside antibiotic resistance in Pseudomonas aeruginosa: a new aminoglycoside 6’-N-acetyl-transferase. Antimicrob Agents Chemother 7:494–499
Kawabe H, Naganawa H, Kondo S, Umezawa H, Mitsuhashi S (1978) New plasmid-mediated phosphorylation of gentamicin C in Staphylococcus aureus. Microbiol Immunol 22:515–521
Kawabe H, Sakurai H, Fukasawa K, Shimizu S, Hasuda K, Iyobe S, Mitsuhashi S (1979) Phosphorylation and inactivation of streptomycin by plant pathogenic Pseudomonas lachrymans. J Antibiot (Tokyo) 32:425–426
Kawaguchi H, Naito T, Nakagawa S, Fujisawa K (1972) BB-K8, a new semisynthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 25:695–708
Kida M, Igarashi S, Okutani T, Asako T, Hiraga K, Mitsuhashi S (1974) Selective phosphorylation of the 5”-hydroxy group of ribostamycin by a new enzyme from Pseudomonas aeruginosa. Antimicrob Agents Chemother 5:92–94
Kida M, Asako T, Yoneda M, Mitsuhashi S (1975) Phosphorylation of dihydrostreptomycin by Pseudomonas aeruginosa. In: Mitsuhashi S (ed) Microbial drug resistance. University of Tokyo Press, Tokyo, pp 441–448
Kobayashi F, Yamaguchi M, Eda J, Higashi F, Mitsuhashi S (1971) Enzymatic inactivation of gentamicin C components by cell-free extract from Klebsiella pneumoniae. J Antibiot (Tokyo) 24:719–721
Kobayashi F, Yamaguchi M, Sato J, Mitsuhashi S (1972) Purification and properties of di-hydrostreptomycin-phosphorylating enzyme from Pseudomonas aeruginosa. Jpn J Microbiol 16:15–19
Kobayashi F, Koshi T, Eda J, Yoshimura Y, Mitsuhashi S, (1973) Lividomycin resistance in staphylococci by enzymatic phosphorylation. Antimicrob Agents Chemother 4:1–5
Kojima M, Ezaki N, Amano S, Inouye S, Niida T (1975) Bioconversion of ribostamycin (SF-733). II. Isolation and structure of 3-N-acetylribostamycin, a microbiologically inactive product of ribostamycin produced by Streptomyces ribosidificus. J Antibiot (Tokyo) 28:42–47
Kondo S (1979) Some chemical modifications of aminoglycoside antibiotics. Jpn J Antibiot 32:S228–S236
Kondo S, Okanishi M, Utahara R, Maeda K, Umezawa H (1968) Isolation of kanamycin and paromamine inactivated by E. coli carrying R factor. J Antibiot (Tokyo) 21:22–29
Kondo S, Yamamoto H, Naganawa H, Umezawa H, Mitsuhashi S (1972) Isolation and characterization of lividomycin A inactivated by Pseudomonas aeruginosa and Escherichia coli carrying R factor. J Antibiot (Tokyo) 25:483–484
Kondo S, Iinuma K, Yamamoto H, Maeda K, Umezawa H (1973a) Synthesis of 1-N-[(S)-4-amino-2-hydroxybutyryl]-kanamycin B and 3’,4’-dideoxykanamycin B active against kanamycin-resistant bacteria. J Antibiot (Tokyo) 26:412–415
Kondo S, Iinuma K, Yamamoto H, Ikeda Y, Maeda K, Umezawa H (1973b) Syntheses of (5)-4-amino-2-hydroxybutyryl derivatives of 3’,4’-dideoxykanamycin B and their antibacterial activities. J Antibiot (Tokyo) 26:705–707
Kondo S, Iinuma K, Hamada M, Maeda K, Umezawa H (1974) Syntheses of isoseryl derivatives of kanamycins and their antibacterial activities. J Antibiot (Tokyo) 27:90–93
Kondo S, Yamamoto H, Iinuma K, Maeda K, Umezawa H (1976) Syntheses of 6’,5”,6”‘-triamino-6’,5”,6”‘-trideoxylividomycin A and 6’5”-diamino-6’,5”-dideoxylividomycin B. J Antibiot (Tokyo) 29:1134–1136
Kondo S, Miyasaka T, Yoshida K, Iinuma K, Umezawa H (1977) Syntheses and properties of kanamycin C derivatives active against resistant bacteria. J Antibiot (Tokyo) 30:1150–1152
Koyama G, Iitaka Y, Maeda K, Umezawa H (1968) The crystal structure of kanamycin. Tetrahedron Lett 1875–1879
Kumar V, Jones GS, Blacksberg I, Remers WA, Misiek M, Pursiano TA (1980) Aminoglycoside antibiotics. 3.Epimino derivatives of neamine, ribostamycin, and kanamycin B. J Med Chem 23:42–49
LeGoffic F (1977) The resistance of S. aureus to aminoglycoside antibiotics and pristinamy-cins in France in 1976–1977. Jpn J Antibiot 30:S286-S291
LeGoffic F, Chevereau M (1972) L’adenyl-gentamycine C1: un derive de la gentamycine inactivée par des bacteries proteuses d’un R-facteur. C R H S Acad Sci, Ser C 274:535–536
LeGoffic F, Martel A (1974) La résistance aux aminosides provoquée par une isoenzyme la kanamycine acétyltransférase. Biochimie 56:893–987
LeGoffic F, Moreau N (1973) Purification by affinity chromatography of an enzyme involved in gentamicin inactivation. FEBS Lett 29:289–291
LeGoffic F, Martel A, Witchitz J (1974) 3-N Enzymatic acetylation of gentamicin, tobramycin and kanamycin by Escherichia coli carrying an R factor. Antimicrob Agents Chemother 6:680–684
LeGoffic F, Martel A, Capmau ML, Baca B, Goebel P, Chardon H, Soussy CJ, Duval J, Bouanchaud DH (1976) New plasmid-mediated nucleotidylation of aminoglycoside antibiotics in Staphylococcus aureus. Antimicrob Agents Chemother 10:258–264
LeGoffic F, Martel A, Moreau N, Capmau ML, Soussy CJ, Duval J (1977) 2”-O-Phosphorylation of gentamicin components by a Staphylococcus aureus strain carrying a plasmid. Antimicrob Agents Chemother 12:26–30
Maeda K, Kondo S, Okanishi M, Utahara R, Umezawa H (1968) Isolation of paromamine inactivated by Pseudomonas aeruginosa. J Antibiot (Tokyo) 21:458–459
Mallams AK, Vernay HF, Crowe DF, Detre G, Tanabe M, Yasuda DM (1973) The synthesis of 4”-deoxygentamicin C1. J Antibiot (Tokyo) 26:782–783
Matsuhashi Y, Yagisawa M, Kondo S, Takeuchi T, Umezawa H (1975) Aminoglycoside 3’-phosphotransferases I and II in Pseudomonas aeruginosa. J Antibiot (Tokyo) 28:442–447
Matsuhashi Y, Sawa T, Takeuchi T, Umezawa H (1976 a) Purification of aminoglycoside 3’-phosphotransferase II. J Antibiot (Tokyo) 29:204–207
Matsuhashi Y, Sawa T, Takeuchi T, Umezawa H (1976b) Immunological studies of aminoglycoside 3’-phosphotransferases. J Antibiot (Tokyo) 29:1127–1128
Matsuhashi Y, Sawa T, Takeuchi T, Umezawa H, Nagatsu I (1976c) Localization of aminoglycoside 3’-phosphotransferase II on a cellular surface of R factor resistant Escherichia coli. J Antibiot (Tokyo) 29:1129–1130
Matsuhashi Y, Sawa T, Kondo S, Takeuchi T (1977) Aminoglycoside 3’-phosphotransferase in Bacillus circulons producing butirosins. J Antibiot (Tokyo) 30:435–437
Mitsuhashi S (1975) Proposal for a rational nomenclature for phenotype, genotype, and aminoglycoside-aminocyclitol modifying enzyme. In: Mitsuhashi S (ed) Drug action and drug resistance in bacteria. 2. Aminoglycoside antibiotics. University of Tokyo Press, Tokyo, pp 269–275
Mitsuhashi S, Kobayashi F, Yamaguchi M (1971) Enzymatic inactivation of gentamicin C components by cell free extract from Pseudomonas aeruginosa. J Antibiot (Tokyo) 24:400–401
Miyamura S (1961) Dysentery bacilli and its relation to the resistance (in Japanese). Nippon Saikingaku Zasshi 16:115–119
Miyasaka T, Ikeda D, Kondo S, Umezawa H (1980) Syntheses and properties of the 6”-deoxy or 4”,6”-dideoxy derivatives of the kanamycin antibiotics. J Antibiot (Tokyo) 33:527–532
Murase M, Ito T, Fukatsu S, Umezawa H (1970) Studies on kanamycin related compounds produced during fermentation by mutants of Streptomyces kanamyceticus. Isolation and properties. Progr Antimicrob Anticancer Chemother 2:1098–1110
Murray BE, Moellering RC Jr (1979) Aminoglycoside-modifying enzymes among clinical isolates of Acinetobacter calcoaceticus subsp.anitratus (Herellea vaginicola): explanation for high-level aminoglycoside resistance. Antimicrob Agents Chemother 15:190–199
Nagabhushan TL, Wright J J, Cooper AB, Turner WN, Miller GH (1978a) Chemical modification of some gentamicins and sisomicin at the 3”-position. J Antibiot (Tokyo) 31:43–54
Nagabhushan TL, Cooper AB, Tsai H, Daniels PJL, Miller GH (1978b) The syntheses and biological properties of l-N-(S-4-amino-2-hydroxybutyryl)-gentamicin B and 1-N-(S-3-amino-2-hydroxypropionyl)-gentamicin B. J Antibiot (Tokyo) 31:681–687
Naganawa H, Kondo S, Maeda K, Umezawa H (1971a) Structure determination of enzymatically phosphorylated products of aminoglycosidic antibiotics by proton magnetic resonance. J Antibiot (Tokyo) 24:823–829
Naganawa H, Yagisawa M, Kondo S, Takeuchi T, Umezawa H (1971b) The structure determination of an enzymatic inactivation product of 3’4’-dideoxykanamycin B. J Antibiot (Tokyo) 24:913–914
Naito T, Nakagawa S, Abe Y, Fujisawa K, Kawaguchi H (1974) Aminoglycoside antibiotics. VIII. Synthesis and activity of 4’-deoxykanamycin A. J Antibiot (Tokyo) 27:838–850
Naito T, Nakagawa S, Toda S, Fujisawa K, Kawaguchi H (1979) Aminoglycoside antibiotics. XIII. Synthesis and activity of 4’-deoxy-6’-N-methylamikacin and related compounds. J Antibiot (Tokyo) 32:659–664
Nara T, Yamamoto M, Kawamoto I, Takayama K, Okachi R, Takasawa S, Sato T, Sato S (1977) Fortimicins A and B, new aminoglycoside antibiotics. I. Producing organism, fermentation and biological properties of fortimicins. J Antibiot (Tokyo) 30:533–540
Neidle S, Rogers D, Hursthouse MB (1968) The crystal and molecular structure of streptomycin oxime selenate. Tetrahedron Lett 4725–4728
Ochiai K, Yamanaka T, Kimura K, Sawada O (1959) Transfer of resistance from resistant dysentery bacteria to E. coli and vice versa in their mixed culture (in Japanese). Nippon Iji Shimpo 1861:34–37
O’Connor S, Lam LKT, Jones ND, Chaney MO (1976) Apramycin, a unique aminocyclitol antibiotic. J Org Chem 41:2087–2092
Okami Y, Hotta K, Yoshida M, Ikeda D, Kondo S, Umezawa H (1979) New aminoglycoside antibiotics, istamycins A and B. J Antibiot (Tokyo) 32:964–966
Okamoto S, Suzuki Y (1965) Chloramphenicol-, dihydrostreptomycin-and kanamycin-in-activating enzymes from multiple drug-resistant Escherichia coli carrying episome “R”. Nature 108:1301–1303
Okanishi M, Kondo S, Suzuki Y, Okamoto S, Umezawa H (1967) Studies on inactivation of kanamycin and resistances of E. coli. J Antibiot (Tokyo) A20:132–135
Okanishi M, Kondo S, Utahara R, Umezawa H (1968) Phosphorylation and inactivation of aminoglycosidic antibiotics by E. coli carrying R factor. J Antibiot (Tokyo) 21:13–21
Ozanne B, Benveniste R, Tipper D, Davies J (1969) Aminoglycoside antibiotics: inactivation by phosphorylation in Escherichia coli carrying R factors. J Bacteriol 100:1144–1146
Richardson K, Jevons S, Moore JW, Ross BC, Wright JR (1977) Synthesis and antibacterial activities of l-N-[(5)-co-amino-2-hydroxyalkyl]kanamycin A derivatives. J Antibiot (Tokyo) 30:843–846
Richardson K, Brammer KW, Jevons S, Plews RM, Wright JR (1979) Synthesis and antibacterial activity of l-N-(l,3-dihydroxy-2-propyl)kanamycin B (UK-31,214). J Antibiot (Tokyo) 32:973–977
Rinehart KL Jr (1964) The neomycins and related antibiotics. John Wiley, New York London Sidney
Rossi D, Goss WA, Daum SJ (1977) Mutational biosynthesis by idiotrophs of Micromono-spora purpurea. I. Conversion of aminocyclitols to new aminoglycoside antibiotics. J Antibiot (Tokyo) 30:88–97
Sano H, Tsuchiya T, Kobayashi S, Hamada M, Umezawa S, Umezawa H (1976) Synthesis of 3”-deoxydihydrostreptomycin active against resistant bacteria. J Antibiot (Tokyo) 29:978–980
Santanam P, Kayser FH (1976) Tobramycin adenylyltransferase: A new aminoglycoside-inactivating enzyme from Staphylococcus epidermidis. J Infect Dis 134:S33-S39
Sato S, Iida T, Okachi R, Shirahata K, Nara T (1977) Enzymatic acetylation of fortimicin A and seldomycin factor 5 by aminoglycoside 3-acetyltransferase I [AAC(3)-I] of E. coli KY8348. J Antibiot (Tokyo) 30:1025–1027
Satoh A, Ogawa H, Satomura Y (1975) Effect of sclerin on production of the aminoglycoside antibiotics accompanied by salvage function in Streptomyces. Agric Biol Chem 39:1593–1598
Smith DH, Janjigian J A, Prescott N, Anderson PW (1970) Resistance factor-mediated spec-tinomycin resistance. Infect Immun 1:120–127
Suami T, Nishiyama S, Ishikawa Y, Umemura E (1978) Modification of aminocyclitol antibiotics. 6. Preparation of 5-deoxykanamycin B. Bull Chem Soc Jpn 51:2354–2357
Suzuki I, Takahashi N, Shirota S, Kawabe H, Mitsuhashi S (1975) Adenylylation of streptomycin by Staphylococcus aureus: a new streptomycin adenylyltransferase. In: Mitsuhashi S (ed) Microbial drug resistance. University of Tokyo Press, Tokyo, pp 463–471
Takagi Y, Miyake T, Tsuchiya T, Umezawa S, Umezawa H (1973) Synthesis of 3’-deoxy-kanamycin B. J Antibiot (Tokyo) 26:403–406
Takasawa S, Utahara R, Okanishi M, Maeda K, Umezawa H (1968) Studies on adenylyl-streptomycin, a product of streptomycin inactivated by E. coli carrying the R factor. J Antibiot (Tokyo) 21:477–484
Tanabe M, Yasuda DM, Detre G (1977) Aminoglycoside antibiotics: synthesis of nebramine, tobramycin and 4”-epi-tobramycin. Tetrahedron Lett 3607–3610
Testa RT, Wagman GH, Daniels PJL, Weinstein MJ (1974) Mutamicins; biosynthetically created new sisomicin analogues. J Antibiot (Tokyo) 27:917–921
Toda S, Nakagawa S, Naito T, Kawaguchi H (1978) Structure determination of amikacin derivatives modified by enzymes from resistant S. aureus strains. Tetrahedron Lett 3917–3920
Tsuchiya T, Jikihara T, Miyake T, Umezawa S, Hamada M, Umezawa H (1979) 3’-Deoxy-amikacin and 3’,4’-dideoxyamikacin and their antibacterial activities. J Antibiot (Tokyo) 32:1351–1353
Umezawa H (1970) Mechanism of inactivation of aminoglycosidic antibiotics by enzymes of resistant organisms of clinical origin. Progr Antimicrob Anticancer Chemother 2:567–571
Umezawa H (1974) Biochemical mechanism of resistance to aminoglycosidic antibiotics. Adv Carbohydr Chem Biochem 30:183–225
Umezawa H (1975) Biochemical mechanism of resistance to aminoglycosidic antibiotics. In: Mitsuhashi S (ed) Drug action and drug resistance in bacteria. 2. Aminoglycoside antibiotics. University of Tokyo Press, Tokyo, pp 211–248
Umezawa H (1979) Studies on aminoglycoside antibiotics: enzymic mechanism of resistance and genetics. Jpn J Antibiot 32:S1–S14
Umezawa H, Ueda M, Maeda K, Yagishita K, Kondo S, Okami Y, Utahara R, Osato Y, Nitta K, Takeuchi T (1957) Production and isolation of a new antibiotic, kanamycin. J Antibiot (Tokyo) A10.181–188
Umezawa H, Okanishi M, Utahara R, Maeda K, Kondo S (1967a) Isolation and structure of kanamycin inactivated by a cell-free system of kanamycin-resistant E. coli. J Antibiot (Tokyo) A20:136–141
Umezawa H, Okanishi M, Kondo S, Hamana K, Utahara R, Maeda K, Mitsuhashi S (1967b) Phosphorylative inactivation of aminoglycosidic antibiotics by Escherichia coli carrying R factor. Science 157:1559–1561
Umezawa H, Takasawa S, Okanishi M, Utahara R, (1968a) Adenylylstreptomycin, a product of streptomycin inactivated by E. coli carrying R factor. J Antibiot (Tokyo) 21:81–82
Umezawa H, Doi O, Ogura M, Kondo S, Tanaka N (1968b) Phosphorylation and inactivation of kanamycin by Pseudomonas aeruginosa. J Antibiot (Tokyo) 21:154–155
Umezawa H, Umezawa S, Tsuchiya T, Okazaki Y (1971) 3’,4’-Dideoxy kanamycin B active against kanamycin-resistant Escherichia coli and Pseudomonas aeruginosa. J Antibiot (Tokyo) 24:485–487
Umezawa H, Nishimura Y, Tsuchiya T, Umezawa S (1972a) Syntheses of 6’-N-methyl-kanamycin and 3’,4’-dideoxy-6’-N-methylkanamycin B active against resistant strains having 6’-N-acetylating enzymes. J Antibiot (Tokyo) 25:743–745
Umezawa H, Tsuchiya T, Muto R, Umezawa S (1972b) Studies on amino sugars. XXIX.-The synthesis of 3’-0-methylkanamycin. Bull Chem Soc Jpn 45:2842–2847
Umezawa H, Yamamoto H, Yagisawa M, Kondo S, Takeuchi T, Chabbert YA (1973a) Kanamycin phosphotransferase I: mechanism of cross-resistance between kanamycin and lividomycin. J Antibiot (Tokyo) 26:407–411
Umezawa H, Yagisawa M, Matsuhashi Y, Naganawa H, Yamamoto H, Kondo S, Takeuchi T, Chabbert YA (1973b) Gentamicin acetyltransferase in Escherichia coli carrying R factor. J Antibiot (Tokyo) 26:612–614
Umezawa H, Matsuhashi Y, Yagisawa M, Yamamoto H, Kondo S, Takeuchi T (1974) Immobilization of phosphotransferases obtained from resistant bacteria. J Antibiot (Tokyo) 27:358–360
Umezawa H, Iinuma K, Kondo S, Hamada M, Maeda K (1975a) Synthesis of 1-N-acyl derivatives of 3’,4’-dideoxy-6’-N-methylkanamycin B and their antibacterial activities. J Antibiot (Tokyo) 28:340–343
Umezawa H, Iinuma K, Kondo S, Maeda K (1975b) Synthesis and antibacterial activity of 6’-N-alkyl derivatives of l-N-[(S)-4-amino-2-hydroxybutyryl]kanamycin. J Antibiot (Tokyo) 28:483–485
Umezawa H, Ikeda D, Miyasaka T, Kondo S (1979) Syntheses and properties of the 6’-C-alkyl derivatives of 3’,4’-dideoxykanamycin B. J Antibiot (Tokyo) 32:1360–1364
Umezawa S, Tsuchiya T, Muto R, Nishimura Y, Umezawa H (1971a) Synthesis of 3’-deoxykanamycin effective against kanamycin-resistant Escherichia coli and Pseudomonas aeruginosa. J Antibiot (Tokyo) 24:274–275
Umezawa S, Tsuchiya T, Jikihara T, Umezawa H (1971b) Synthesis of 3’,4’-dideoxyneamine active against kanamycin-resistant E. coli and P. aeruginosa. J Antibiot (Tokyo) 24:711–712
Umezawa S, Jikihara T, Tsuchiya T, Umezawa H (1972a) Syntheses of 3’-and 4’-0-methylneamine. J Antibiot (Tokyo) 25:322–324
Umezawa S, Tsuchiya T, Ikeda D, Umezawa H (1972b) Syntheses of 3’,4’-dideoxy and 3’,4’,5”-trideoxyribostamycin active against kanamycin-resistant E. coli and P. aeruginosa. J Antibiot (Tokyo) 25:613–616
Umezawa S, Watanabe I, Tsuchiya T, Umezawa H, Hamada M (1972c) Synthesis of 5”-deoxylividomycin B. J Antibiot (Tokyo) 25:617–618
Umezawa S, Ikeda D, Tsuchiya T, Umezawa H (1973) Synthesis of l-N-((S)4-amino-2-hy-droxybutyryl)-3’,4’-dideoxyneamine. J Antibiot (Tokyo) 26:304–306
Umezawa S, Nishimura Y, Hata Y, Tsuchiya T, Yagisawa M, Umezawa H (1974) Synthesis of 4’-deoxykanamycin and its resistance to kanamycin phosphotransferase II. J Antibiot (Tokyo) 27:722–725
Umezawa Y, Yagisawa M, Sawa T, Takeuchi T, Umezawa H, Matsumoto H, Tazaki T (1975) Aminoglycoside 3’-phosphotransferase III. A new phosphotransferase in resistance mechanism. J Antibiot (Tokyo) 28:845–853
Usui T, Tsuchiya T, Umezawa S (1978) 1-and 3-Deamidino derivatives of dihydrostreptomycin and some 1-N-acyl derivatives. J Antibiot (Tokyo) 31:991–996
Vastola AP, Altschaefl J, Harford S (1980) 5-epi-Sisomicin and 5-epi-gentamicin B: substrates for aminoglycoside-modifying enzymes that retain activity against aminogly-coside-resistant bacteria. Antimicrob Agents Chemother 17:798–802
Waitz J A, Miller GH, Moss E Jr, Chiu PJS (1978) Chemotherapeutic evaluation of 5-episi-somicin (Sch 22591), a new semisynthetic aminoglycoside. Antimicrob Agents Chemother 13:41–48
Walker JB, Skorvaga M (1973) Phosphorylation of streptomycin and dihydrostreptomycin by Streptomyces. Enzymatic synthesis of different diphosphorylated derivatives. J Biol Chem 248:2435–2440
Watanabe I, Tsuchiya T, Umezawa S, Umezawa H (1973a) Synthesis of l-N-((S)-4-amino-2-hydroxybutyryl)lividomycin A. J Antibiot (Tokyo) 26:310–312
Watanabe I, Tsuchiya T, Umezawa S, Umezawa H (1973b) Syntheses of 6’-amino-6’-deoxy-lividomycin B and 6’-deoxy-6’-methylamino-and 6’-deoxy-6’-P-hydroxyethylamino)-lividomycin B. J Antibiot (Tokyo) 26:802–804
Watanabe I, Tsuchiya T, Nakamura F, Hamada M, Umezawa S (1978) Synthesis of 5”-amino-3’,5”-dideoxybutirosin A. J Antibiot (Tokyo) 31:863–867
Watanabe I, Deushi T, Yamaguchi T, Kamiya K, Nakayama M, Mori T (1979) The structural elucidation of aminoglycoside antibiotics, sannamycins A and B. J Antibiot (Tokyo) 32:1066–1068
Williams JW, Northrop DB (1976) Purification and properties of gentamicin acetyltrans-ferase I. Biochemistry 15:125–131
Williams JW, Northrop DB (1978a) Kinetic mechanisms of gentamicin acetyltransferase I. Antibiotic-dependent shift from rapid to nonrapid equilibrium random mechanisms. J Biol Chem 253:5902–5907
Williams JW, Northrop DB (1978b) Substrate specificity and structure-activity relationships of gentamicin acetyltransferase. I. Dependence of antibiotic resistance upon substrate Vmax/Km values. J Biol Chem 253:5908–5914
Witchitz JL (1972) Plasmid-mediated gentamicin resistance not associated with kanamycin resistance in Enterobacteriaceae. J Antibiot (Tokyo) 25:622–624
Woo PWK (1975) 5”-Amino-3’,4’,5”-trideoxybutirosin A, a new semi-synthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 28:522–529
Wright JJ (1976) Synthesis of 1-N-ethylsisomicin: a broad-spectrum semisynthetic aminoglycoside antibiotic. J Chem Soc Chem Commun 206–208
Wright JJ, Cooper A, Daniels PJL, Nagabhushan TL, Rane D, Turner WN, Weinstein J (1976) Selective N-acylation of gentamicin antibiotics. Synthesis of 1-N-acyl derivatives. J Antibiot (Tokyo) 29:714–719
Yagisawa M, Naganawa H, Kondo S, Hamada M, Takeuchi T, Umezawa H (1971) Adeny-lyldideoxykanamycin B, a product of the inactivation of dideoxykanamycin B by Escherichia coli carrying R factor. J Antibiot (Tokyo) 24:911–912
Yagisawa M, Naganawa H, Kondo S, Takeuchi T, Umezawa H (1972a) Inactivation of 3’,4’-dideoxykanamycin B by an enzyme solution of resistant E. coli and isolation of 3’,4’-dideoxykanamycin B 2”-guanylate and 2”-inosinate. J Antibiot (Tokyo) 25:492–494
Yagisawa M, Naganawa H, Kondo S, Takeuchi T, Umezawa H (1972b) 6’-N-Acetylation of 3’,4’-dideoxykanamycin B by an enzyme in a resistant strain of Pseudomonas aeruginosa. J Antibiot (Tokyo) 25:495–496
Yagisawa M, Yamamoto H, Naganawa H, Kondo S, Takeuchi T, Umezawa H (1972c) A new enzyme in Escherichia coli carrying R factor phosphorylating 3’-hydroxyl of butirosin A, kanamycin, neamine and ribostamycin. J Antibiot (Tokyo) 25:748–750
Yagisawa M, Kondo S, Takeuchi T, Umezawa H (1975) Aminoglycoside 6’-N-acetyltrans-ferase of Pseudomonas aeruginosa: structural requirements of substrate. J Antibiot (Tokyo) 28:486–489
Yamada T, Tipper D, Davies J (1968) Enzymatic inactivation of streptomycin by R factor-resistant Escherichia coli. Nature 219:288–291
Yamaguchi M, Mitsuhashi S, Kobayashi F, Zenda H (1974) A 2’-N-acetylating enzyme of aminoglycosides. J Antibiot (Tokyo) 27:507–515
Yamamoto H, Kondo S, Maeda K, Umezawa H (1972a) Synthesis of lividomycin A 5”-phosphate, an enzymatically inactivated lividomycin A. J Antibiot (Tokyo) 25:485–486
Yamamoto H, Kondo S, Maeda K, Umezawa H (1972b) Synthesis of 5”-deoxylividomy-cin A and its amino derivatives. J Antibiot (Tokyo) 25:487–488
Yamamoto H, Yagisawa M, Naganawa H, Kondo S, Takeuchi T, Umezawa H (1972c) Kanamycin 6’-acetate and ribostamycin 6’-acetate, enzymatically inactivated products by Pseudomonas aeruginosa. J Antibiot (Tokyo) 25:746–747
Yano H, Fujii H, Mukoo H, Shimura M, Watanabe T, Sekizawa Y (1978) On the enzymatic inactivation of dihydrostreptomycin by Pseudomonas lachrymans, cucumber angular leaf spot bacterium: isolation and structural resolution of the inactivated product. Ann Phytopathol Soc Jpn 44:413–419
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1982 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Umezawa, H., Kondo, S. (1982). Mechanisms of Resistance to Aminoglycoside Antibiotics. In: Umezawa, H., Hooper, I.R. (eds) Aminoglycoside Antibiotics. Handbook of Experimental Pharmacology, vol 62. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-68579-8_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-68579-8_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-68581-1
Online ISBN: 978-3-642-68579-8
eBook Packages: Springer Book Archive