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AAC Accepts, published online ahead of print on 16 October 2006
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Antimicrob. Agents Chemother. doi:10.1128/AAC.00739-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Effect of anaerobic growth on quinolone lethality with Escherichia coli

Muhammad Malik, Syed Hussain, and Karl Drlica*

Public Health Research Institute, 225 Warren Street, Newark, NJ 07103


   Abstract

Quinolone activity was examined with Escherichia coli during aerobic growth, aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid, norfloxacin, ciprofloxacin, and PD161144 were lethal with cultures growing aerobically, and the bacteriostatic activity of each quinolone was unaffected by anaerobic growth. However, lethal activity was distinct for each quinolone with cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic acid failed to kill under both conditions, norfloxacin killed cells when grown anerobically but not when treated with chloramphenicol, ciprofloxacin killed cells under both conditions but required higher concentations than with cells grown aerobically, and PD161144, a C-8-methoxy fluoroquinolone, was equally lethal under all conditions. Following pretreatment with nalidixic acid, a shift to anaerobic conditions or addition of chloramphenicol rapidly blocked further cell death. Formation of quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS)-dependent drop in cell lysate viscosity, occurred during aerobic or anaerobic growth and in the presence or absence of chloramphenicol. However, lethal chromosome fragmentation, detected as a drop in viscosity in the absence of SDS, occurred with nalidixic acid treatment only under aerobic conditions in the absence of chloramphenicol. With PD161144, chromosome fragmentation was detected with cells grown aerobically or anaerobically and in the presence or absence of chloramphenicol. Thus all quinolones tested appear to form reversible bacteriostatic complexes containing broken DNA during aerobic growth, anaerobic growth, and when protein synthesis is blocked; however, the ability to fragment chromosomes and to rapidly kill cells under these conditions depends on quinolone structure.




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