Bactericidal effect against <i>Escherichia coli</i> of nalidixic acid and four structurally related compounds

Stevens, P.

doi:10.1093/jac/6.4.535

Cited by 24 publications

(18 citation statements)

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“…First, killing appears to involve DNA gyrase, because quinolone resistance mutations in the gyrA gene of DNA gyrase result in increased drug concentrations necessary to kill bacteria (3,6,29). Also, a gyrA mutant strain of E. coli selected with nalidixic acid appears to be partially tolerant to quinolones (6,29).…”

Section: Discussionmentioning

confidence: 99%

“…Also, a gyrA mutant strain of E. coli selected with nalidixic acid appears to be partially tolerant to quinolones (6,29). Second, bacterial killing by quinolones is blocked by chloramphenicol, rifampin, 2,4-dinitrophenol, or nutrient starvation (6,9,27,29,35), all of which inhibit protein synthesis, suggesting that synthesis of a protein may be required for quinolone killing.…”

Section: Discussionmentioning

confidence: 99%

“…Second, bacterial killing by quinolones is blocked by chloramphenicol, rifampin, 2,4-dinitrophenol, or nutrient starvation (6,9,27,29,35), all of which inhibit protein synthesis, suggesting that synthesis of a protein may be required for quinolone killing. Such a requirement may explain the paradoxical effect of decreased killing of some bacterial strains by high concentrations of quinolone (7,10,27,29,32), because low drug concentrations inhibit DNA synthesis, whereas high concentrations inhibit RNA and protein synthesis as well (14,29,32). There are, in addition, differences in bactericidal activity among quinolones.…”

Section: Discussionmentioning

confidence: 99%

“…There are, in addition, differences in bactericidal activity among quinolones. Analog 17606 is only bacteriostatic (29), and ofloxacin and ciprofloxacin, in comparison with norfloxacin and nalidixic acid, produce greater killing of E. coli in the presence of chloramphenicol (27) or nutrient starvation (35).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of quinolone killing apart from the involvement of DNA gyrase (3,6,29) remains largely unknown. To gain further insight into quinolone killing, we isolated and characterized a strain of E. coli inhibited but inefficiently killed by (i.e., tolerant to) quinolones.…”

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confidence: 99%

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Isolation and characterization of an Escherichia coli strain exhibiting partial tolerance to quinolones

Wolfson

Hooper

Shih

et al. 1989

Antimicrob Agents Chemother

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Quinolone antimicrobial agents rapidly kill bacteria by largely unknown mechanisms. To study this phenomenon, a strain of Escherichia coli inhibited but inefficiently killed by (i.e., partially tolerant to) norfloxacin was isolated and characterized. E. coli KL16 (norfloxacin MIC, 0.10 ,ug/ml; MBC, 0.20 ,Ig/ml) was mutagenized with nitrosoguanidine and cyclically exposed to 3 ,zg of norfloxacin per ml. After five cycles, a bacterial strain (DS1) which was killed 1,000-fold less than KL16 during 3 h of drug exposure was isolated. The MIC and MBC of norfloxacin for DS1 were 0.20 and 1.5 ,ug/ml, respectively. Over a range of norfloxacin concentrations, DS1 was killed 2 to 4 orders of magnitude less than KL16. DS1 grew more slowly than KL16 but after normalization for growth rate was killed four times less rapidly than KL16 at drug concentrations 10-fold higher than respective MICs. DS1 and KL16 cells ifiamented similarly upon exposure to norfloxacin. DS1 exhibited tolerance to other DNA gyrase A subunit antagonists (ofloxacin and ciprofloxacin) and DNA gyrase B subunit antagonists (novobiocin and coumermycin) but not to the aminoglycoside gentamicin, suggesting involvement of DNA gyrase. DS1 also appeared to be minimally tolerant to the P-lactam cefoxitin.DS1 exhibited increased susceptibility to the mutagen methyl methanesulfonate, implying a defect in DNA repair. This report describes the first use of quinolone enrichment for isolation of a bacterial strain partially tolerant to quinolones. The study of defects in such tolerant strains offers an approach to an increased understanding of the mechanisms of bacterial killing by quinolones.

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