Question

Mutations to the alpha subunit of DNA gyrase may cause bacterial resistance to which drug? (A) trimethoprim (B) gatifloxacin (C) sulfamethoxazole (D) daptomycin (E) nitrofurantoin

Short answer

Gatifloxacin (B) is the drug affected by mutations in DNA gyrase.

Step-by-step solution

Understand the Role of DNA Gyrase

DNA gyrase is an enzyme that is crucial in the supercoiling of bacterial DNA, which is important for DNA replication and transcription processes. Some antibiotics target DNA gyrase to inhibit these processes, thus preventing bacterial growth and survival.

Identify the Class of Drugs Affecting DNA Gyrase

The class of drugs known to target DNA gyrase is fluoroquinolones. These drugs work by inhibiting bacterial DNA gyrase, leading to the prevention of DNA replication and transcription, ultimately causing bacterial cell death.

Match the Options with Fluoroquinolones

Review the given options: (A) trimethoprim, (B) gatifloxacin, (C) sulfamethoxazole, (D) daptomycin, (E) nitrofurantoin. Out of these options, gatifloxacin belongs to the class of fluoroquinolones.

Conclude the Drug Linked with DNA gyrase Resistance

Since gatifloxacin (option B) is a fluoroquinolone that targets DNA gyrase, mutations in the alpha subunit of DNA gyrase can lead to bacterial resistance specifically against gatifloxacin.

Key concepts

DNA gyrase

DNA gyrase is a vital bacterial enzyme involved in the process of DNA supercoiling. Supercoiling is necessary to compact the large DNA molecule into the confined spaces of a bacterial cell. Without supercoiling, DNA replication and transcription could become inefficient or impossible.

DNA gyrase plays a role in relieving torsional strain created ahead of the replication fork during DNA replication. It introduces negative supercoils into DNA using energy from ATP.

Since DNA gyrase is not present in humans, it becomes an attractive target for antibacterial drugs aimed specifically at bacteria.

Fluoroquinolones

Fluoroquinolones are a class of broad-spectrum antibiotics that target bacterial DNA gyrase. These antibiotics interfere with the DNA replication process. By binding to the enzyme, they inhibit its activity leading to the prevention of bacterial DNA replication and ultimately to bacterial cell death.

Common examples of fluoroquinolones include ciprofloxacin, levofloxacin, and gatifloxacin. They are often used to treat a variety of bacterial infections, including respiratory, urinary tract, and gastrointestinal infections.

• Strong effectiveness against a wide range of bacteria
• Works by targeting bacterial DNA gyrase
• Key tool in combating bacterial infections

Resistance can develop if bacteria mutate the target of the drug, the DNA gyrase itself.

Antibiotic resistance

Antibiotic resistance is a growing problem in medicine and public health. It occurs when bacteria change in a way that reduces or eliminates the effectiveness of drugs designed to cure or prevent infections.

Bacterial mutations in DNA gyrase, such as those in the alpha subunit, can lead to resistance against fluoroquinolones. When this happens, the drug can no longer effectively bind to its target, making the antibiotic less effective.

• Arises from mutations in bacterial DNA
• Lowers the effectiveness of antibiotics
• Can lead to difficult-to-treat bacterial infections

Combating resistance requires responsible antibiotic use and ongoing research for new treatments.

Bacterial DNA replication

Bacterial DNA replication is the process through which a bacterial cell makes a copy of its DNA before cell division. This process is crucial for bacterial growth and proliferation.

DNA gyrase plays a significant role in facilitating this by relieving torsional strain ahead of the replication fork. This allows for the smooth progression of the replication process.

• Essential for cell division
• Involves several key enzymes, including DNA gyrase
• Targets for antibiotics like fluoroquinolones

Inhibiting key enzymes like DNA gyrase can effectively halt bacterial replication.

Supercoiling of DNA

Supercoiling is the over-winding or under-winding of a DNA strand. In bacteria, supercoiling condenses the DNA structure, making it more compact. This is essential for fitting the DNA into the small bacterial cell.

DNA gyrase is one of the primary enzymes responsible for the negative supercoiling of bacterial DNA. This configuration is necessary for efficient and accurate DNA replication and transcription.

• Maintains compact DNA structure
• Allows DNA to fit inside bacterial cells
• Facilitates smooth DNA replication

Proper regulation of supercoiling is critical for bacterial survival and growth.