Name: fluoroquinolone antibiotics and bacterial dna
Uploaded: 2026-03-12T13:36:01.000Z
Duration: 1 min 28 s
Channel: JoVE

Bacteria rely on precise and rapid DNA replication to multiply and spread infection.Fluoroquinolones are synthetic antibiotics that target two enzymes essential for bacterial DNA synthesis: DNA gyrase and topoisomerase IV.During replication, DNA gyrase introduces negative supercoils in the chromosome.It works by making a cut in the DNA strands, passing the other DNA segments through the cut, and sealing the DNA again.After replication, topoisomerase IV cuts the DNA strands to separate the two circular daughter chromosomes.To inhibit this process, fluoroquinolones trap these enzyme-DNA complexes in their cleaved state.The accumulation of double-stranded DNA fragments disrupts essential cellular processes, leading to bacterial cell death.Fluoroquinolones primarily inhibit DNA gyrase in Gram-negative bacteria, while topoisomerase IV is the main target in Gram-positive bacteria.Due to this selectivity, fluoroquinolones are widely used as broad-spectrum antibiotics to treat infections caused by both Gram-positive and Gram-negative bacteria.

inhibitors of bacterial dna synthesis

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases&#8212;DNA gyrase and topoisomerase&#8239;IV&#8212;are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA&#8211;enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively toxic to bacteria due to structural differences between bacterial and eukaryotic topoisomerases.Fluoroquinolones offer broad-spectrum coverage against both Gram-negative and Gram-positive pathogens, including intracellular organisms such as Legionella and Mycoplasma, due to efficient cellular uptake via porins.Specific agents like ciprofloxacin, levofloxacin, and moxifloxacin are employed in urinary tract infections, respiratory infections, skin and soft tissue infections, osteomyelitis (e.g., Salmonella in sickle cell patients), and hospital-acquired pneumonia.Side Effects Although fluoroquinolones are generally well tolerated, they are associated with several rare but serious adverse effects.<ul><li>Tendinitis and tendon rupture, particularly involving the Achilles tendon, are notable complications, with a higher incidence in elderly patients and those receiving corticosteroids.</li><li>Central nervous system side effects are diverse, ranging from mild symptoms such as headache and insomnia to severe manifestations including seizures, psychosis, and, in rare instances, suicidal ideation.</li><li>Peripheral neuropathy is another concern, with some cases resulting in irreversible nerve damage.</li><li>Fluoroquinolones have been linked to an increased risk of aortic aneurysm and dissection, particularly among older adults with preexisting vascular disease.</li><li>Gastrointestinal complications, such as Clostridioides difficile&#8211;associated colitis, are comparable in frequency to those seen with other broad-spectrum antibiotics.</li></ul>Pharmacovigilance Due to these serious adverse effects and rapidly emerging resistance, fluoroquinolones are now generally reserved for conditions where benefits outweigh risks, or when first-line agents are ineffective. Regulatory bodies such as the FDA and EMA recommend limited use for uncomplicated infections and emphasize antimicrobial stewardship to minimize resistance development and adverse outcomes.

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases&#8212;DNA gyrase and ...

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Education

JoVE Core

Microbiology

Unit

Antimicrobial Agents

KEY TERMS AND CONCEPTS

fluoroquinolone antibiotics and bacterial dna

Fluoroquinolone antibiotics target bacterial DNA replication by blocking two key type II topoisomerases: DNA gyrase and topoisomerase IV. These enzymes help bacteria manage DNA supercoiling and separate chromosomes during replication. When they are disrupted, bacterial pathogens cannot copy DNA efficiently and infection can spread less effectively.

Fluoroquinolones are synthetic versions of quinolones. They work by stabilizing the short-lived DNA-enzyme cleavage complex, which stops strand religation, or rejoining of DNA strands. This leads to lethal double-strand breaks. These drugs are selectively toxic to bacteria because bacterial and eukaryotic topoisomerases are structurally different.

These antibiotics have broad-spectrum activity against Gram-negative and Gram-positive bacteria. They can also reach intracellular organisms such as Legionella and Mycoplasma because they enter cells efficiently through porins. Common examples include ciprofloxacin, levofloxacin, and moxifloxacin. They are used for urinary tract infections, respiratory infections, skin and soft tissue infections, osteomyelitis such as Salmonella infection in sickle cell patients, and hospital-acquired pneumonia.

Fluoroquinolones are generally well tolerated, but they can cause rare yet serious side effects. Tendinitis and tendon rupture, especially in the Achilles tendon, are important risks and occur more often in elderly patients and in people taking corticosteroids. Side effects can also affect the central nervous system, with symptoms ranging from headache and insomnia to seizures, psychosis, and, rarely, suicidal ideation.

Other concerns include peripheral neuropathy, which may cause irreversible nerve damage in some cases. These drugs have also been linked to a higher risk of aortic aneurysm and dissection, especially in older adults with preexisting vascular disease. Gastrointestinal problems, including Clostridioides difficile–associated colitis, occur at rates similar to those seen with other broad-spectrum antibiotics.

Because of these adverse effects and rapidly growing resistance, fluoroquinolones are now usually reserved for infections where the benefits outweigh the risks or when first-line treatments do not work. Regulatory agencies such as the FDA and EMA recommend limiting use for uncomplicated infections. They also stress antimicrobial stewardship to reduce resistance and avoid preventable harm.

Fluoroquinolone Antibiotics and Bacterial DNA

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Fluoroquinolone antibiotics target bacterial DNA replication by blocking two key type II topoisomerases: DNA gyrase and topoisomerase IV. These enzymes help bacteria manage DNA supercoiling and separate chromosomes during replication. When they are disrupted, bacterial pathogens cannot copy DNA efficiently and infection can spread less effectively. Fluoroquinolones are synthetic versions of quinolones. They work by stabilizing the short-lived DNA-enzyme cleavage complex, which stops strand...

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key terms and concepts

Learn how fluoroquinolone antibiotics block bacterial DNA replication, their common uses, and why doctors reserve them because of serious side effects and resistance.

Fluoroquinolone Antibiotics and Bacterial DNA | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

Fluoroquinolone Antibiotics and Bacterial DNA

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