How Does Ciprofloxacin Destroy The Enzymes In Bacteria?

Ciprofloxacin is an antibiotic used to treat various infections by converting two bacterial enzymes, topoisomerase IV and DNA gyrase, into toxic enzymes that block the manufacture and repair of DNA and other DNA processes. It belongs to the group of medicines known as fluoroquinolones (quinolones). The ultimate mechanism of action remains unknown, but the increasing incidence of ciprofloxacin-resistant pathogens threatens the continued empiric use of ciprofloxacin and calls for the development of novel ciprofloxacin derivatives.

Floroquinolones, like ciprofloxacin, have two bacterial drug targets, DNA gyrase and DNA topoisomerase IV (3,4), both essential enzymes. These enzymes are sequenced differently, and antibiotics like ciprofloxacin can specifically target specific enzymes. Three postulates define antibiotic efficacy in the context of bacterial metabolism: antibiotics alter the metabolic state of bacteria, which contributes to cell death; bactericidal antibiotics kill bacteria by inhibiting essential cellular processes and activating cellular response pathways that contribute to cell death; ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and can reduce the clearance of drugs metabolized by that enzyme; and ciprofloxacin is a potent suppressor of DNA gyrase, creating a complex structure with the enzyme and cleaved DNA.

Ciprofloxacin works by inhibiting bacterial DNA gyrase and topoisomerase IV, two critical enzymes necessary for bacterial DNA. It can specifically target an enzyme called DNA gyrase in bacteria, which relaxes tightly wound chromosomal DNA, allowing DNA replication and repair.

How do antibiotics inhibit bacterial protein synthesis?

Some examples of macrolide antibiotics are clarithromycin, azithromycin, and erythromycin. Macrolides inhibit bacterial protein synthesis by preventing polypeptide chains from forming. They do this by attaching to the 50S subunit of the bacterial ribosome and blocking the tunnel that the polypeptide chain exits from.

What is the mechanism of resistance to ciprofloxacin in E. coli?

The mechanisms of ciprofloxacin resistance in E. coli have been investigated intensively in the past 30 years. Mutations in genes coding for DNA gyrase and topoisomerase IV contribute to ciprofloxacin resistance in E. coli. 10, 11 In addition, efflux pumps may decrease drug accumulation while peptides and enzymes may block drug targets or may modify the drug, respectively (Figure 1). Numerous reviews have covered the topic of ciprofloxacin resistance in E. coli, but these reviews have been overwhelmingly qualitative in nature. 12–19.

Schematic representation of four mechanisms of ciprofloxacin resistance in E. coli. (a) Target alteration. (b) Decreased ciprofloxacin accumulation. (c) Physical blocking of ciprofloxacin target. (d) Enzymatic modification of ciprofloxacin.

With the rapidly increasing availability of next generation sequencing technologies, research aimed at the prediction of a resistance phenotype from genomic data is increasing. However, these efforts typically correlate genotypic data with a categorical measure of resistance, whereas a quantitative resistance phenotype prediction is of clinical relevance. Therefore, we carried out a systematic review, summarizing observational and experimental studies that assessed genetic ciprofloxacin resistance determinants and the ciprofloxacin MIC conferred by these determinants in E. coli, to elucidate how the presence of genomic resistance determinants, either alone or in combination, affects ciprofloxacin MIC in E. coli. In addition, we performed an E. coli protein network analysis to detect potential additional determinants of ciprofloxacin resistance based on the findings of the systematic review.

What is the mechanism of action of ciprofloxacin on bacteria?

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase.

Explore a selection of our essential drug information below, or:

Description An antibiotic used to treat a wide variety of infections in the body.

Description An antibiotic used to treat a wide variety of infections in the body.

How does ciprofloxacin work?

Ciprofloxacin is an antibiotic. It belongs to a group of antibiotics called fluoroquinolones. It works by killing the bacteria that causes an infection.

Ciprofloxacin is a broad-spectrum antibiotic which means that it’s used to treat a number of bacterial infections, such as:

• Uncomplicated urinary tract infections (UTIs) where other antibiotics are not suitable and complicated UTIs
• chest infections (including pneumonia )
• skin and bone infections
• sexually transmitted infections (STIs)
• conjunctivitis
• eye infections
• ear infections
• infections that other antibiotics have been unable to treat

It is also used to help prevent people getting meningitis if they have been in close contact with someone with the infection.

It comes as tablets, a liquid that you drink, ear drops and eye drops. It’s also given by injection, but this is usually done in hospital.

What is the mechanism of action of ciprofloxacin resistance?

Ciprofloxacin acts by binding to its targets, DNA gyrase and topoisomerase IV, inhibiting the native ability of these two enzymes to re-ligate double stranded DNA breaks, in turn leading to fragmentation of the chromosome.

PERSPECTIVE article. Front. Microbiol., 02 July 2018.

This article is part of the Research Topic Antibiotic Alternatives and Combinational Therapies for Bacterial Infections View all 21 articles.

• 1 Department of Biology, Section for Functional Genomics, University of Copenhagen, Copenhagen, Denmark
• 2 Department of Veterinary and Animal Sciences, Section for Veterinary Clinical Microbiology, University of Copenhagen, Copenhagen, Denmark
• 3 Department of Clinical Microbiology, Center for Diagnostics, Rigshospitalet, Copenhagen, Denmark

Does ciprofloxacin inhibit CYP450?

Various drugs may inhibit the CYP450 system. Among the quinolone antibiotics, ciprofloxacin has been demonstrated in vitro to be one of the more potent of these inhibitors, 5 affecting in particular CYP1A2 and CYP3A4. 5, 6 However, the clinical response is sometimes difficult to predict, and the significance of the interaction differs among patients.

This report describes a patient who was receiving a stable dose of methadone for treatment of heroin addiction and in whom severe respiratory depression developed after initiation of ciprofloxacin for aspiration pneumonia.

CASE REPORT. A man in his mid-50s * presented to hospital with fracture of the left ankle after the bicycle he was riding was struck by a car. His blood pressure was 170/90 mm Hg, heart rate 75/min, and respiratory rate 18/min. The patient had a history of hepatitis A, and both alkaline phosphatase (134 U/L; normal range 45–125 U/L) and γ-glutamyl transferase (594 U/L; normal range 10–50 U/L) were elevated. He was a smoker (3–4 packs/day) and had previously been an injection drug user (heroin and cocaine), for which methadone 50 mg PO once daily had been prescribed for at least 6 months before the current admission. He denied use of any other medication.

Does ciprofloxacin inhibit bacterial protein synthesis?

Abstract. Ciprofloxacin is a new fluoroquinolone that is highly active against many diverse microorganisms. At concentrations of less than 1 microgram/mL it is active against most gram-negative bacteria, including Enterobacteriaceae, Haemophilus, Neisseria, and other Pasteurellaceae, Vibrionaceae, and various species of Pseudomonas and Acinetobacter. Most staphylococci, including strains resistant to methicillin, are also susceptible to ciprofloxacin. Streptococci are not highly susceptible to ciprofloxacin, and obligate anaerobes are generally resistant to this and other quinolones. Ciprofloxacin, like other quinolones, inhibits DNA gyrase, but its bactericidal effects are not completely reversible by inhibitors of protein or RNA synthesis. Thus, unlike many other quinolones, ciprofloxacin may have multiple lethal effects. Resistance is less readily selected in vitro by ciprofloxacin than by nalidixic acid, and single-step mutants usually remain susceptible to clinically achievable concentrations. Resistance mediated by mutations in genes altering DNA gyrase and expression of outer membrane proteins has been described for ciprofloxacin and other quinolones. The antimicrobial spectrum and potency of ciprofloxacin, coupled with its rapid bactericidal effects, make this fluoroquinolone a promising new antimicrobial agent.

Sanders CC. Sanders CC. Clin Infect Dis. 1992 Feb;14:526-38. doi: 10. 1093/clinids/14. 2. 526. Clin Infect Dis. 1992. PMID: 1554842 Review.

The comparative in-vitro activity of eight newer quinolones and nalidixic acid.

How does the antibiotic ciprofloxacin work?

Ciprofloxacin is an antibiotic. It belongs to a group of antibiotics called fluoroquinolones. It works by killing the bacteria that causes an infection.

Ciprofloxacin is a broad-spectrum antibiotic which means that it’s used to treat a number of bacterial infections, such as:

• Uncomplicated urinary tract infections (UTIs) where other antibiotics are not suitable and complicated UTIs
• chest infections (including pneumonia )
• skin and bone infections
• sexually transmitted infections (STIs)
• conjunctivitis
• eye infections
• ear infections
• infections that other antibiotics have been unable to treat

It is also used to help prevent people getting meningitis if they have been in close contact with someone with the infection.

It comes as tablets, a liquid that you drink, ear drops and eye drops. It’s also given by injection, but this is usually done in hospital.

What bacteria are killed with ciprofloxacin?

Ciprofloxacin is a broad-spectrum antibiotic that inhibits DNA gyrase, specifically topoisomerase II and topoisomerase IV, which is responsible for resealing the DNA double-strand. This mechanism of action can lead to exonucleolytic degradation, as single-stranded DNA may be affected. Ciprofloxacin has been found to affect several Gram-positive bacteria, including Staphylococcus, Streptococcus, Enterococcus, Bacillus spp., and Mycobacterium. It also shows acceptable in vitro activity against most Gram-negative bacteria strains, including Enterobacteriaceae, N. gonorrhoeae, Neisseria meningitides, Haemophilus influenza, Moraxella catarrhalis, P. aeruginosa, and Legionella species. A study ranked the in vitro activities of seven FQs against 140 clinical Acinetobacter baumannii isolates in the order of clinafloxacin gatifloxacin, levofloxacin, trovafloxacin gemifloxacin, moxifloxacin ciprofloxacin, and moxifloxacin ciprofloxacin.

Ciprofloxacin’s mechanisms of action involve slowed DNA replication and the creation of double-stranded DNA breaks. Its clinical usage is presented in Tables 1, 2, and 13. The study suggests further confirmation of these findings in further studies.

How does ciprofloxacin inhibit DNA replication?

Ciprofloxacin, a new fluoroquinolone, is a potent, broad-spectrum antibacterial agent. It rapidly blocks bacterial deoxyribonucleic acid (DNA) replication by inhibiting DNA gyrase, an essential prokaryotic enzyme that catalyzes chromosomal DNA supercoiling.

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