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. 2018 Mar 1;14(3):e1006805.
doi: 10.1371/journal.ppat.1006805. eCollection 2018 Mar.

Wicked: The untold story of ciprofloxacin

Zachary C Conley  1   2 , Truston J Bodine  2   3   4 , Andrew Chou  2   5 , Lynn Zechiedrich  1   2   3   4   6
Affiliations

Wicked: The untold story of ciprofloxacin

Zachary C Conley et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Ciprofloxacin MICs of E. coli clinical isolates.
Box and whisker plots show the range of ciprofloxacin MICs for FQS and FQR clinical isolates. Data are from Becnel Boyd et al. 2009 [12]. Plots are divided into four quartiles, each representing 25% of the MICs (Q1: end of lower whisker to edge of box; Q2: edge of box to median line; Q3: median line to edge of box; Q4: edge of box to end of upper whisker). The length of the box is referred to as the IQR. Circles indicate outliers (here MICs higher than Q4 plus 1.5x IQR). Ciprofloxacin-susceptible isolates (MIC ≤1 μg/ml), as determined in the microbiology laboratory of the hospital; ciprofloxacin-nonsusceptible isolates were categorized as FQR. CIP, ciprofloxacin; FQR, fluoroquinolone-resistant; FQS, fluoroquinolone-susceptible; IQR, interquartile range; MIC, minimum inhibitory concentration.
Fig 2
Fig 2. Schematic showing known ciprofloxacin resistance mechanisms in E. coli.
(A) Ciprofloxacin-susceptible E. coli. The inner and outer membranes intrinsically protect the bacterium. Also depicted are the AcrAB-TolC efflux pump, porin, and DNA gyrase (or topoisomerase IV) interacting with the DNA nucleoid (in blue). Ciprofloxacin (green diamond) can diffuse through the membranes but also accesses the cell via porins. Ciprofloxacin forms a ternary complex with the topoisomerase bound to DNA, resulting in cell death. (B) Chromosomally encoded ciprofloxacin resistance mechanisms. Altered porin(s), mutant gyrase (and perhaps also topoisomerase IV), and increased numbers of AcrAB-TolC efflux pumps are shown. Ciprofloxacin access is reduced via alterations (deletion, down-regulation, or mutation) in porins. Ciprofloxacin that enters the cell can be removed through increased numbers of efflux pumps. Ciprofloxacin that reaches the mutant topoisomerase(s) is less effective against the mutant version of the enzyme than the drug-susceptible version shown in A. (C) Plasmid-borne ciprofloxacin resistance mechanisms. Plasmids can harbor genes encoding the ciprofloxacin efflux pumps QepA or OqxAB, the Qnr protein—which binds gyrase by mimicking B-form DNA—or Aac(6’)-Ib-cr, an aminoglycoside-modifying acetyltransferase that acetylates and inactivates ciprofloxacin. Aac(6’)-Ib-cr, aminoglycoside 6’-N-acetyltransferase type lb-cr; AcrAB-TolC, Acriflavin-resistant Proteins AB Tolerant to Colicin E mutant; OqxAB, olaquindox-resistant efflux pump proteins A and B; QepA, quinolone efflux pump A; Qnr, quinolone resistance protein.
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References

    1. Levin K, Cashore B, Bernstein S, Auld G. Overcoming the tragedy of super wicked problems: constraining our future selves to ameliorate global climate change. Policy Sci. 2012;45: 123–152. doi: 10.1007/s11077-012-9151-0 - DOI
    1. Roberts N. Wicked problems and network approaches to resolution. Int Public Manag Rev. 2000;1: 1–19.
    1. Khodursky AB, Zechiedrich EL, Cozzarelli NR. Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci U S A. 1995;92: 11801–11805. - PMC - PubMed
    1. Kreuzer KN, Cozzarelli NR. Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth. J Bacteriol. 1979;140: 424–435. - PMC - PubMed
    1. Bush NG, Evans-Roberts K, Maxwell A. DNA topoisomerases. EcoSal Plus. 2015;6 doi: 10.1128/ecosalplus.ESP-0010-2014 - DOI - PubMed

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