Effect of Nalidixic Acid and Hydroxyurea on Division Ability ofEscherichia coli fil+andlon−Strains

Kantor, George J.; Deering, R. A.

doi:10.1128/jb.95.2.520-530.1968

Cited by 57 publications

(25 citation statements)

References 21 publications

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“…S1 A-G). Residual nalidixic acid is unlikely to contribute to the ROSmediated killing on agar, because quinolone-gyrase-DNA complexes are reversible, and washing cells to remove quinolone fully restores DNA synthesis blocked by formation of the complexes (31)(32)(33); if the complexes are rendered irreversible by crosslinking of quinolone to gyrase, DNA synthesis is not restored (32). In addition, a mass spectrometry-based assay showed that washing and diluting cells lowered intracellular quinolone concentration to 0.002 times MIC (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

Post-stress bacterial cell death mediated by reactive oxygen species

Hong

Zeng

Wang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

324

253

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Antimicrobial efficacy, which is central to many aspects of medicine, is being rapidly eroded by bacterial resistance. Since new resistance can be induced by antimicrobial action, highly lethal agents that rapidly reduce bacterial burden during infection should help restrict the emergence of resistance. To improve lethal activity, recent work has focused on toxic reactive oxygen species (ROS) as part of the bactericidal activity of diverse antimicrobials. We report that when Escherichia coli was subjected to antimicrobial stress and the stressor was subsequently removed, both ROS accumulation and cell death continued to occur. Blocking ROS accumulation by exogenous mitigating agents slowed or inhibited poststressor death. Similar results were obtained with a temperature-sensitive mutational inhibition of DNA replication. Thus, bacteria exposed to lethal stressors may not die during treatment, as has long been thought; instead, death can occur after plating on drug-free agar due to poststress ROS-mediated toxicity. Examples are described in which (i) primary stress-mediated damage was insufficient to kill bacteria due to repair; (ii) ROS overcame repair (i.e., protection from anti-ROS agents was reduced by repair deficiencies); and (iii) killing was reduced by anti-oxidative stress genes acting before stress exposure. Enzymatic suppression of poststress ROS-mediated lethality by exogenous catalase supports a causal rather than a coincidental role for ROS in stress-mediated lethality, thereby countering challenges to ROS involvement in antimicrobial killing. We conclude that for a variety of stressors, lethal action derives, at least in part, from stimulation of a self-amplifying accumulation of ROS that overwhelms the repair of primary damage.reactive oxygen species | poststress cellular response | antimicrobial | antioxidant | damage repair D iscovering ways to manage antimicrobial resistance is among the most important medical challenges of our time (1). Since many antimicrobials can stimulate the production of resistant mutants, often via the SOS response (2-8), one way to limit the emergence of new resistance is to more rapidly and extensively reduce pathogen populations during infection. Toward that end, we and others have been studying how antimicrobials and other lethal stressors kill bacteria. Recent work has drawn attention to the contribution of stress-stimulated accumulation of toxic reactive oxygen species (ROS) (9-21). Finding ways to stimulate ROS-mediated killing could in principle enhance the efficacy of a broad range of antimicrobials. However, an ROS contribution to antimicrobial killing became controversial when the original observation (9) was challenged (22-24). Subsequent work countered many of the challenges (13)(14)(15)25) and extended the phenomenon to thymineless death (26), phage infection (27), the type VI secretion system (27), and overexpression of a MalE-LacZ fusion (28). Moreover, nitric oxide and hydrogen sulfide interfere with antimicrobial killing by suppressing ROS generation/ac...

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Section: Resultsmentioning

confidence: 99%

Post-stress bacterial cell death mediated by reactive oxygen species

Hong

Zeng

Wang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

324

253

View full text Add to dashboard Cite

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“…This compound, or a closely related derivative, probably also acts in the regulation of cell division (9). Both prophage induction and cell division seem to be intimately related to some phase of the DNA replication cycle (2,8).…”

Section: Discussionmentioning

confidence: 99%

Cell Division and Prophage Induction inEscherichia coli: Effects of Pantoyl Lactone and Various Furan Derivatives

1972

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Strain T-44 is a thermosensitive mutant of Escherichia coli in which both cell division and prophage repression are altered at elevated temperatures. The effects of various ribosides, pantoyl lactone, and the furfural derivatives nitrofurazone and 5-methyl furfural suggest that some low-molecular-weight compound is important in the control of cell division and prophage repression in this strain. This low-molecular-weight compound may have a five-membered oxygen-containing ring as part of its structure.on July 31, 2020 by guest

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“…When the nalidixic acid concentration is above the minimum inhibitory concentration (MIC), DNA synthesis is blocked. However, promptly after the nalidixic acid is washed away, DNA synthesis resumes (12). Based on mass spectrometry quantification, Hong et al (10) measure a decrease in intracellular nalidixic acid concentration to 0.002 MIC after washing and diluting treated cells.…”

Section: Time After Addition Of Antibioticmentioning

confidence: 99%