Mode of action of a new nalidixic acid derivative, AB206

Nagate, Takatoshi; Komatsu, Teiko; Izawa, A; Ohmura, Shigeo; Namiki, Shinjuro; Mitsuhashi, Susumu

doi:10.1128/aac.17.5.763

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…Here we show that in permeabilized P. aeruginosa cells, DNA replication is sensitive to NAL; the NAL concentration needed to give 50% inhibition (ID50) of DNA synthesis was very similar to that reported for permeabilized E. coli (24). Hence, it seems that the cell envelope critically influences the different susceptibilities of these bacteria to NAL.…”

supporting

confidence: 47%

“…In the wild-type PAO strains, the NAL concentration required to bring about ID50 of replicative DNA synthesis was about 10 jig/ml (Table 3). The corresponding ID50s reported for toluenized cells of E. coli and Serratia marcescens are 13.6 and 2.6 j.g/ml, respectively (24). Thus, in vitro the replicative DNA syntheses of these three organisms show similar sensitivities to NAL.…”

Section: Resultsmentioning

confidence: 57%

“…In E. coli, NAL inhibits replicative DNA synthesis (8,24); the target is the DNA gyrase subunit A (6, 7). Here we show that in permeabilized P. aeruginosa cells, DNA replication is sensitive to NAL; the NAL concentration needed to give 50% inhibition (ID50) of DNA synthesis was very similar to that reported for permeabilized E. coli (24).…”

mentioning

confidence: 99%

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Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes

Rella¹,

Haas²

1982

Antimicrob Agents Chemother

166

120

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Resistance to high concentrations of nalidixic acid in Pseudomonas aeruginosa PAO was due to mutations in one locus designated nalA, which was mapped by transduction between hex-9001 and leu-10. The nalA mutants were cross-resistant to pipemidic acid, a nalidixic acid analog, at relatively low concentrations. Replicative DNA synthesis was resistant to both drugs in permeabilized cells of nalA mutants. A locus coding for low-level resistance to nalidixic acid, nalB, was cotransducible with pyrB, proC, and met-28. The nalB mutants were also resistant to low levels of pipemidic acid, novobiocin, and P-lactam antibiotics (e.g., carbenicillin, azlocillin, and cefsulodin), but not to other drugs, such as gentamicin, rifampin, kanamycin, or tetracycline. In nalB mutants, DNA replication showed wild-type sensitivity to nalidixic acid, whereas carbenicillin-induced filamentation required higher drug levels than in the wild-type strain. Thus, nalB mutations appear to decrease cell permeability to some antibiotics. The sensitivity of replicative DNA synthesis to nalidixic acid and novobiocin was very similar in P. aeruginosa and Escherichia coli; by contrast, the concentrations of these drugs needed to inhibit growth of P. aeruginosa were higher than those reported for E. coli by one or two orders of magnitude.

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supporting

confidence: 47%

Section: Resultsmentioning

confidence: 57%

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Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes

Rella¹,

Haas²

1982

Antimicrob Agents Chemother

166

120

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“…To confirm this possibility, we compared the uptake of norfloxacin by cells of the wild-type strain and the two porin-deficient mutants. The uptake of norfloxacin by the bacterial cells was measured by the method of Nagate et al (11) with the following modifications. Cells were grown to mid-log phase at 37°C in antibiotic medium 3 (Difco Laboratories), and a bacterial cell suspension (A570 = 0.7) was prepared with the same medium.…”

mentioning

confidence: 99%

Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli

Hirai¹,

Aoyama²,

Irikura³

et al. 1986

Antimicrob Agents Chemother

Self Cite

230

140

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The mechanism of penetration of quinolones through the bacterial outer membrane was studied with lipopolysaccharide-deficient and porin-deficient mutants. The data indicated that the lipopolysaccharide layer might form a permeability barrier for hydrophobic quinolones such as nalidixic acid but not for hydrophilic quinolones such as norfloxacin and ciprofloxacin. The results also showed that quinolones with a low relative hydrophobicity appeared to permeate through OmpF porin, whereas quinolones with a high relative hydrophobicity appeared to permeate through both OmpF porin and phospholipid bilayers.New quinolone derivatives which have broader and more potent antibacterial activity against gram-negative and grampositive bacteria than old quinolones, such as nalidixic acid, have recently been developed. They also have greater antibacterial activity against nalidixic acid-resistant bacteria (5,7,9,21,24,25).We previously reported that the greater antibacterial activity of norfloxacin, one of these new quinolones, might be due to its greater ability to permeate bacterial cells and its potent inhibitory action on in vivo DNA synthesis (5).The ability of drugs to pass through the bacterial outer membrane is a very important factor in their antibacterial activity and spectrum (2,10,13,14,22,23,26). There are many reports on the penetration into bacterial cells of various antimicrobial agents, especially beta-lactam antibiotics (4,8,15,22,23,26), but the penetration mechanisms of quinolones have not been studied in detail.We report here on the mechanisms of penetration of quinolones through the bacterial outer membrane with lipopolysaccharide ( ofloxacin were from Daiichi Pharmaceutical Co. Ltd.; pipemidic acid, piromidic acid, and enoxacin were from Dainippon Pharmaceutical Co. Ltd.; and ciprofloxacin was from Bayer Yakuhin Co. Ltd. The partition coefficients of the quinolones were determined by the modified method of Nikaido (13). Solutions (10 ,ug/ml) of quinolones were made in 0.1 M phosphate buffer (pH 7.2). After shaking with an equal volume of n-octanol at 25°C for 48 h and centrifuging at 1,870 x g for phase separation, the concentrations of quinolones in the aqueous phase were determined with spectrophotometric assay by measuring the A272 for enoxacin, norfloxacin, and pefloxacin, the A286 for ciprofloxacin, the A264 for pipemidic acid, the A288 for cinoxacin, the A292 for AM-833 and piromidic acid, the A294 for ofloxacin, the A264 for miloxacin, the A290 for oxolinic acid, the A258 for nalidixic acid, the A285 for rosoxacin, and the A254 for flumequine. The partition coefficients were expressed as the ratio of the amount of compound in the n-octanol phase to that in the aqueous phase.Susceptibility to quinolones was measured by the agar dilution method with Mueller-Hinton agar and an inoculum of 106 CFU per spot as described previously (7). The data were expressed as MICs.We tested the antibacterial activity of quinolones against LPS-deficient (rfa) mutants of S. typhimurium LT2 (19) ( Table 1). The suscepti...

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“…on RNA and protein synthesis (8, 12,15). Oxolinic acid and AB206 also inhibit DNA synthesis in Escherichia coli (11,14). To examine whether pipemidic acid inhibits DNA synthesis of the L-form, the incorporation of radioactive thymidine, uracil, and L-leucine into trichloroacetic acid-insoluble material was measured.…”

mentioning

confidence: 99%

The Effect of Pipemidic Acid on the Growth of a Stable L‐Form of Staphylococcus aureus

Yabu¹,

Tomizu²,

Kanda

1984

Microbiology and Immunology

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Mode of action of a new nalidixic acid derivative, AB206

Cited by 9 publications

References 17 publications

Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes

Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes

Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli

The Effect of Pipemidic Acid on the Growth of a Stable L‐Form of Staphylococcus aureus

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