Lack of Interaction of Fluoroquinolones with Lipopolysaccharides

Lindner, Buko; Wiese, Andre; Brandenburg, Klaus; Seydel, Ulrich; Dalhoff, A.

doi:10.1128/aac.46.5.1568-1570.2002

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…This proposed mechanism is similar to that of EDTA (37,41). However, this hypothesis has been disputed, and recently, Lindner and colleagues have shown that quinolones do not chelate cations from their LPSbinding sites (25). It must be noted that purified LPS does not necessarily mimic the complex environment of the OM, and therefore, care should be taken to directly extrapolate the findings obtained with purified LPS to whole bacteria (33).…”

Section: Resultsmentioning

confidence: 99%

Quinolones Sensitize Gram-Negative Bacteria to Antimicrobial Peptides

Campos

Morey

Bengoechea

2006

Antimicrob Agents Chemother

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The treatment of infections caused by bacteria resistant to the vast majority of antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the front line of defense in those areas exposed to microorganisms, and there is intensive research to explore their use as new antibacterial agents. On the other hand, it is known that subinhibitory concentrations of antibiotics affect the expression of numerous bacterial traits. In this work we evaluated whether treatment of bacteria with subinhibitory concentrations of quinolones may alter the sensitivity to APs. A 1-h treatment of Klebsiella pneumoniae with 0.25؋ the MIC of ciprofloxacin rendered bacteria more sensitive to polymyxins B and E, human neutrophil defensin 1, and ␤-defensin 1. Levofloxacin and nalidixic acid at 0.25؋ the MICs also increased the sensitivity of K. pneumoniae to polymyxin B, whereas gentamicin and ceftazidime at 0.25؋ the MICs did not have such an effect. Ciprofloxacin also increased the sensitivities of K. pneumoniae ciprofloxacin-resistant strains to polymyxin B. Two other pathogens, Pseudomonas aeruginosa and Haemophilus influenzae, also became more sensitive to polymyxins B and E after treatment with 0.25؋ the MIC of ciprofloxacin. Incubation with ciprofloxacin did not alter the expression of the K. pneumoniae loci involved in resistance to APs. A 1-N-phenyl-naphthylamine assay showed that ciprofloxacin and levofloxacin increased the permeabilities of the K. pneumoniae and P. aeruginosa outer membranes, while divalent cations antagonized this action. Finally, we demonstrated that ciprofloxacin and levofloxacin increased the binding of APs to the outer membrane by using dansylated polymyxin B.

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Section: Resultsmentioning

confidence: 99%

Quinolones Sensitize Gram-Negative Bacteria to Antimicrobial Peptides

Campos

Morey

Bengoechea

2006

Antimicrob Agents Chemother

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“…). The permeation of fluoroquinolones and tetracyclines through the self‐promoted uptake pathway is debated in the literature . Self‐promoted uptake is most often determined by one of two assays.…”

Section: Gram‐negative Bacteria Are Impermeable To Most Small Moleculesmentioning

confidence: 99%

The challenge of converting Gram‐positive‐only compounds into broad‐spectrum antibiotics

Richter

Hergenrother

2018

Annals of the New York Academy of Sciences

188

202

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Multidrug resistant Gram-negative bacterial infections are on the rise, and there is a lack of new classes of drugs to treat these pathogens. This drug shortage is largely due to the challenge of finding antibiotics that can permeate and persist inside Gram-negative species. Efforts to understand the molecular properties that enable certain compounds to accumulate in Gram-negative bacteria based on retrospective studies of known antibiotics have not been generally actionable in the development of new antibiotics. A recent assessment of the ability of >180 diverse small molecules to accumulate in Escherichia coli led to predictive guidelines for compound accumulation in E. coli. These "eNTRy rules" state that compounds are most likely to accumulate if they contain a nonsterically encumbered ionizable Nitrogen (primary amines are the best), have low Three-dimensionality (globularity ≤ 0.25), and are relatively Rigid (rotatable bonds ≤ 5). In this review, we look back through 50+ years of antibacterial research and 1000s of derivatives and assess this historical data set through the lens of these predictive guidelines. The results are consistent with the eNTRy rules, suggesting that the eNTRy rules may provide an actionable and general roadmap for the conversion of Gram-positive-only compounds into broad-spectrum antibiotics.

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“…Moxifloxacin has not yet been studied in this respect. However, it could not be demonstrated that ciprofloxacin or moxifloxacin were incorporated into LPS or displaced cations from LPS [57].…”

Section: Introductionmentioning

confidence: 97%

Immunomodulatory Activities of Fluoroquinolones

2005

Self Cite

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A review of published data on the in vitro, ex vivo, in vivo and clinical effects of fluoroquinolones on the synthesis of cytokines is provided. Fluoroquinolones (FQs) were found to affect both cellular and humoral immunity. In general, FQs exert their modulating effects only when used together with a co-stimulant. The in vitro studies generated heterogeneous data because of inhomogeneous effects triggered by different types of co-stimulants and differing responses of various cell lines on the stimuli. However, there is the general trend that FQs decrease the synthesis of pro-inflammatory cytokines. Studies in experimental animals generated homogenous data. All the FQs studied exerted significant clinical effects by attenuating cytokine responses in vivo. The FQs were found to be effective in vivo either in infections caused by organisms against which these are inactive or when dosed suboptimally, so that serum levels were lower than the susceptibilities of the causative pathogens. These in vivo effects were correlated with a significant decrease in pro-inflammatory cytokines like Il-1 and TNF. In addition, FQs were found to upregulate hematopoiesis. These immunomodulatory effects can be attributed in particular to those FQs with a cyclopropyl-moiety at the position N1 of the quinolone core structure, i. e. ciprofloxacin, moxifloxacin, grepafloxacin, sparfloxacin. The immunomodulatory effects of the FQs are due to their effects on intracellular cyclic AMP and phosphodiesterases, on transcription factors such as NF-kappa B, activator protein 1 and a triggering effect on the eucaryotic equivalent of bacterial SOS response. All these studies indicate that FQs exert immunomodulatory activities in particular in latent or chronic infections.

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Lack of Interaction of Fluoroquinolones with Lipopolysaccharides

Cited by 13 publications

References 35 publications

Quinolones Sensitize Gram-Negative Bacteria to Antimicrobial Peptides

Quinolones Sensitize Gram-Negative Bacteria to Antimicrobial Peptides

The challenge of converting Gram‐positive‐only compounds into broad‐spectrum antibiotics

Immunomodulatory Activities of Fluoroquinolones

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