Rifamycins Mechanism of Action

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Questions and Answers

What is the name of the ring structure found in macrolides?

Sugar residue ring

Ribosome binding ring

Macrocyclic lactone ring (correct)

Cyclic peptide ring

How do macrolides function in preventing protein production?

By targeting the outer membrane of bacteria

By targeting the cytoplasm of bacteria

By targeting ribosomes and preventing protein production (correct)

By targeting DNA replication and transcription

What is one mechanism of resistance to macrolides?

Enhanced protein production

Improved cell wall synthesis

Increased DNA replication

Inhibition of drug entry and accumulation (correct)

What is the name of the gene that encodes an efflux pump that impairs accumulation of macrolides?

mef gene Signup and view all the answers

What is the effect of methylation of the ribosome in bacteria?

Resistance to macrolides, clindamycin, and streptogramins Signup and view all the answers

What is the name of the gene that encodes an enzyme that methylates the ribosome binding site?

erm gene Signup and view all the answers

What is the effect of mutations that occur in the ribosome binding site?

Resistance to macrolides Signup and view all the answers

What is the consequence of resistance to one member of the macrolide group?

Resistance to other macrolides Signup and view all the answers

What is the mechanism of action of rifamycins?

They inhibit bacterial RNA polymerase and block elongation of mRNA Signup and view all the answers

Why are rifamycins often used in combination with other agents?

To prevent the emergence of resistant strains Signup and view all the answers

What is the consequence of a single mutation in the bacterial gene that encodes RNA polymerase?

The bacterium becomes resistant to rifamycins Signup and view all the answers

Which rifamycin is most commonly used to treat staphylococcal infections?

Rifampin Signup and view all the answers

What is the advantage of using rifampin alone in prophylaxis against Neisseria meningitidis and Haemophilus influenzae?

The chance of a rifampin-resistance mutation is minimized Signup and view all the answers

Why is rifabutin preferred over rifampin in individuals being treated for tuberculosis and HIV infection?

It inhibits the cytochrome P-450 system to a lesser degree Signup and view all the answers

What is the structure of rifamycins?

An aromatic nucleus linked to an aliphatic handle on both ends Signup and view all the answers

What is the effect of rifampin on the cytochrome P-450 system?

It induces the cytochrome P-450 system Signup and view all the answers

What is the mechanism of action of lincosamide antibiotics?

They bind to the 50S subunit of the bacterial ribosome and inhibit protein synthesis Signup and view all the answers

Why are lincosamide antibiotics used as adjunctive therapy in toxic shock syndrome?

Because they inhibit protein synthesis, preventing toxin production Signup and view all the answers

What is the reason for clindamycin's resistance to some strains of bacteria?

Ribosomal modification Signup and view all the answers

What type of bacteria is clindamycin most active against?

Aerobic gram-positive bacteria and anaerobic bacteria Signup and view all the answers

What is the major toxicity of clindamycin?

Clostridium difﬁcile colitis Signup and view all the answers

What is the primary mechanism by which tetracyclines interact with the bacterial ribosome?

By preventing binding by tRNA molecules loaded with amino acids Signup and view all the answers

What is the reason for Clostridium difﬁcile overgrowth in the bowel?

Clindamycin's ability to kill many components of the normal bacterial ﬂora in the bowel Signup and view all the answers

What is the name of the related class of antibiotics to which tigecycline belongs?

Glycylcyclines Signup and view all the answers

What is pseudomembranous colitis characterized by?

Plaques of necrotic debris lining the colon Signup and view all the answers

Which of the following is a common mechanism of resistance to tetracyclines?

Acquisition of exogenous genes that encode efﬂux pumps Signup and view all the answers

What is the name of the structure that allows tetracyclines to interact with the bacterial ribosome?

Four fused six-membered rings Signup and view all the answers

What is another side effect of clindamycin besides Clostridium difﬁcile colitis?

Diarrhea not caused by C. difﬁcile Signup and view all the answers

Which of the following is NOT a member of the tetracycline class of antibiotics?

Azithromycin Signup and view all the answers

What is the result of the interaction between tetracyclines and the bacterial ribosome?

Protein synthesis is blocked Signup and view all the answers

What is the function of ribosomal protection proteins in bacterial resistance to tetracyclines?

They alter the conformation of the bacterial ribosome Signup and view all the answers

Which of the following tetracycline antibiotics has been recently approved for use?

Tigecycline Signup and view all the answers

What is linezolid?

A completely synthetic antibacterial agent Signup and view all the answers

How does linezolid prevent protein synthesis?

By inhibiting the formation of the first peptide bond Signup and view all the answers

Why are some aerobic gram-negative bacilli resistant to linezolid?

Because they produce efflux pumps active against linezolid Signup and view all the answers

What is the mechanism of resistance to linezolid?

A single amino acid mutation within the gene encoding a portion of the ribosome Signup and view all the answers

What type of bacteria is linezolid active against?

Most aerobic gram-positive bacteria Signup and view all the answers

Which of the following bacteria is linezolid not active against?

Some aerobic gram-negative bacilli Signup and view all the answers

What is the name of the class of antibacterial agents that linezolid belongs to?

Oxazolidinones Signup and view all the answers

What is the unique feature of linezolid's structure?

It has a unique oxazolidinone core modified at several sites Signup and view all the answers

Study Notes

Rifamycins

Rifamycins have a similar structure that includes an aromatic nucleus linked by an aliphatic "handle" on both ends.
They inhibit bacterial RNA polymerase by nestling deep into the DNA/RNA tunnel of the enzyme and sterically blocking elongation of the nascent mRNA molecule.
Resistance to rifamycins develops easily and can result from single mutations in the bacterial gene that encodes RNA polymerase, which change only a single amino acid at the site where the rifamycins bind to RNA polymerase.
Rifamycins are usually used in combination with other agents to prevent the emergence of resistant strains.
Rifampin is used in combination regimens for the treatment of mycobacterial infections and is also effective as monotherapy for prophylaxis against Neisseria meningitidis and Haemophilus influenzae.

Macrolides

Macrolides consist of a large cyclic core called a macrocyclic lactone ring, which is decorated with sugar residues.
They bind tightly to the 50S subunit of the bacterial ribosome at a location that blocks the exit of the newly synthesized peptide, preventing protein production.
Resistance to macrolides occurs by one of several mechanisms, including:
- Inhibition of drug entry and accumulation, which can be mediated by efﬂux pumps.
- Enzyme-mediated ribosome binding site alteration, which can be encoded by genes such as the erm gene in S.pneumoniae.
- Mutation of the ribosome binding site, which is a rare mechanism.
Resistance to one member of the macrolide group usually implies resistance to all members.
Macrolides are active against various bacteria, including Streptococcus pneumoniae and Haemophilus influenzae.

Tetracyclines and Glycylcyclines

Tetracyclines have a core structure consisting of four fused six-membered rings, which allows them to interact with the 30S subunit of the bacterial ribosome and prevent binding by tRNA molecules loaded with amino acids.
Resistance to tetracyclines occurs by one of two mechanisms:
- Acquisition of exogenous genes that encode efﬂux pumps, which prevent intracellular accumulation of these drugs.
- Acquisition of genes that encode ribosomal protection proteins, which alter the conformation of the bacterial ribosome such that tetracyclines no longer bind.
Tigecycline is a glycylcycline antibiotic that has recently been approved for use.

Lincosamides

Lincosamide antibiotics bind to the 50S subunit of the bacterial ribosome and inhibit protein synthesis.
Clindamycin's mechanism of action is very similar to that of the macrolides, and its binding sites overlap with those of the macrolides.
Clindamycin is active against two groups of bacteria: aerobic gram-positive bacteria and anaerobic bacteria, including staphylococci and streptococci.
Clindamycin is not useful against aerobic gram-negative bacteria due to its inability to penetrate their outer membranes.

Linezolid

Linezolid is a synthetic antibiotic that binds to the 50S subunit of the bacterial ribosome, preventing association of this subunit with the 30S subunit and inhibiting protein synthesis.
Resistance to linezolid has already been detected and is the consequence of a single amino acid mutation within the gene encoding a portion of the ribosome.
Linezolid has excellent activity against most aerobic gram-positive bacteria, including methicillin-resistant staphylococci, penicillin-resistant S.pneumoniae, and vancomycin-resistant enterococci.
Some aerobic gram-negative bacilli, such as Escherichia coli, are intrinsically resistant to linezolid due to the production of efﬂux pumps active against this compound.

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Description

This quiz covers the mechanism of action of rifamycins, including how they inhibit bacterial RNA polymerase and the development of resistance.