Norfloxacin, the first of a new class of fluoroquinolone antimicrobials, revisited

Gadebusch, Hans H.; Shungu, D L

doi:10.1016/0924-8579(91)90019-a

Cited by 14 publications

(5 citation statements)

References 244 publications

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“…Thus, it is rational to speculate that the upregulation of these genes will increase the survival of cells upon treatment with antibiotics that are capable of causing oxidative damage. To test our speculation, norfloxacin, a fluoroquinolone, inhibits DNA replication via affecting the activity of DNA gyrase, was used in the killing assay (Gadebusch and Shungu 1991). The norfloxacin MIC of EcN wildtype and derivatives was 1 μg/ mL.…”

Section: Transcriptional Interruption Of Ccdab and Hipab Affects The Expression Of Genes Involved In Stress Responsementioning

confidence: 99%

Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917

Xia

et al. 2020

Appl Microbiol Biotechnol

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Toxin-antitoxin systems (TASs) have attracted much attention due to their important physiological functions. These small genetic factors have been widely studied mostly in commensal Escherichia coli strains, whereas the role of TASs in the probiotic E. coli Nissle 1917 (EcN) is still elusive. Here, the physiological role of chromosomally encoded type II TASs in EcN was examined. We showed that gene pair ECOLIN_00240-ECOLIN_00245 and ECOLIN_08365-ECOLIN_08370 were two functional TASs encoding CcdAB and HipAB, respectively. The homologs of CcdAB and HipAB were more conserved in E. coli species belonging to pathogenic groups, suggesting their important roles in EcN. CRISPRi-mediated repression of ccdAB and hipAB significantly reduced the biofilm formation of EcN in the stationary phase. Moreover, ccdAB and hipAB were shown to be responsible for the persister formation in EcN. Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. Besides, CRISPRi was proposed to be an efficient tool in annotating multiple TASs simultaneously. Collectively, our results advance knowledge and understanding of the role of TASs in EcN, which will enhance the utility of EcN in probiotic therapy. Key points• Two TASs in EcN were identified as hipAB and ccdAB.• Knockdown of HipAB and CcdAB resulted in decreased biofilm formation of EcN.• Transcriptional silencing of hipAB and ccdAB affected the persister formation of EcN.• An attractive link between TASs and stress response was unraveled in EcN.• CRISPRi afforded a fast and in situ annotation of multiple TASs simultaneously.

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Section: Transcriptional Interruption Of Ccdab and Hipab Affects The Expression Of Genes Involved In Stress Responsementioning

confidence: 99%

Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917

Xia

et al. 2020

Appl Microbiol Biotechnol

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“…Norfloxacin is widely used in the treatment of infectious conditions such as urinary tract infections, 46 prostate, skin, pulmonary and digestive infections. [47][48][49] It belongs to the fluoroquinolone family of drugs that target bacterial enzymes involved in DNA replication thereby inhibiting cell division. 50 The exact mechanism of its action, particularly from its uptake by the membrane through drug-lipid interactions to drug-DNA complex formation however is not well established.…”

Section: Introductionmentioning

confidence: 99%

Dependence of norfloxacin diffusion across bilayers on lipid composition

2016

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Antibiotic resistance is a growing concern in medicine and raises the need to develop and design new drug molecules that can efficiently inhibit bacterial replication. Spurring the passive uptake of the drug molecules is an obvious solution. However our limited understanding of drug-membrane interactions due to the presence of an overwhelming variety of lipids constituting cellular membranes and the lack of facile tools to probe the bio-physical interactions between drugs and lipids imposes a major challenge towards developing new drug molecules that can enter the cell via passive diffusion. Here, we used a label-free micro-fluidic platform combined with giant unilamellar lipid vesicles to investigate the permeability of membranes containing mixtures of DOPE and DOPG in DOPC, leading to a label-free measurement of passive membrane-permeability of autofluorescent antibiotics. A fluoroquinolone drug, norfloxacin was used as a case study. Our results indicate that the diffusion of norfloxacin is strongly dependent on the lipid composition which is not expected from the traditional octanol-lipid partition co-efficient assay. The anionic lipid, DOPG, slows the diffusion process whereas the diffusion across liposomes containing DOPE increases with higher DOPE concentration. Our findings emphasise the need to investigate drug-membrane interactions with focus on the specificity of drugs to lipids for efficient drug delivery, drug encapsulation and targeted drug-delivery.

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“…Their mechanism of action is believed to be inhibition of DNA gyrase, preventing both replication and repair of DNA, affecting both actively growing (replication) and more slowly growing cells (repair processes). Fluoroquinolone activity, which is blocked by chloramphenicol, dinitrophenol, and amino acid starvation, requires both new protein synthesis and a functioning electron transport system (3,4,6,18).…”

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confidence: 99%

Increased susceptibility of Pseudomonas aeruginosa to ciprofloxacin in the presence of vancomycin

Day¹,

Marceau-Day²,

Day³

1993

Antimicrob Agents Chemother

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Vancomycin in combination with ciprofloxacin exhibited synergy against 7 of 10 strains of Pseudomonas aeruginosa. MICs for the microbial strains used in this study ranged from 0.0325 to 3.0 micrograms/ml for ciprofloxacin and from 23.5 to > 188 micrograms/ml for vancomycin. Combinations of these antibiotics, tested in a checkerboard pattern, gave fractional inhibitory concentrations of 0.5 or less for 7 of the 10 strains tested.

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Norfloxacin, the first of a new class of fluoroquinolone antimicrobials, revisited

Cited by 14 publications

References 244 publications

Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917

Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917

Dependence of norfloxacin diffusion across bilayers on lipid composition

Increased susceptibility of Pseudomonas aeruginosa to ciprofloxacin in the presence of vancomycin

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