Mechanism Of Action Of Antibiotics

1. A 65-year-old woman was admitted to the emergency room with altered consciousness, fever (103.6° F), nausea and vomiting.. Vital signs on admission were: blood pressure 90/50 mm Hg , pulse 115 bpm, respirations 20/min. Physical examination showed a patient in obvious distress with stiff neck and positive Brudzinski's sign. Pupils were equal, poorly reactive to light and papilledema was present. An empirical IV therapy was started with ampicillin, ceftriaxone and vancomycin. Which of the following phrases best explains the mechanism of action common to all the given drugs?

Misreading of mRNA template code

Inhibition of tetrahydrofolate synthesis

Inhibition of RNA polymerization

Blockade of peptidyl-tRNA translocation

Inhibition of peptidoglycan synthesis

Learning objective: Explain the mechanism of action common to ampicillin, ceftriaxone and
vancomycin.
Answer: E
The signs and symptoms of the patient strongly suggest the diagnosis of meningitis. When the
patient is very ill and the offending organism is unknown an empiric triple antibiotic therapy is
usually given, pending CSF test results. Third generation cephalosporins like ceftriaxone are active
against most gram positive and gram negative bacteria. Since many MR resistant cocci are
increasingly prevalent, vancomycin is usually added. Ampicillin is added to cover Listeria species.
All these antibiotic act by inhibiting the synthesis of peptidoglycan. Ampicillin and ceftriaxone inhibit
the transpeptidation reaction so blocking the cross link formation. Vancomycin inhibits
transglycosylase, so blocking further elongation of peptidoglycan chain.

Explanation

Learning objective: Explain the mechanism of action common to ampicillin, ceftriaxone and
vancomycin.
Answer: E
The signs and symptoms of the patient strongly suggest the diagnosis of meningitis. When the
patient is very ill and the offending organism is unknown an empiric triple antibiotic therapy is
usually given, pending CSF test results. Third generation cephalosporins like ceftriaxone are active
against most gram positive and gram negative bacteria. Since many MR resistant cocci are
increasingly prevalent, vancomycin is usually added. Ampicillin is added to cover Listeria species.
All these antibiotic act by inhibiting the synthesis of peptidoglycan. Ampicillin and ceftriaxone inhibit
the transpeptidation reaction so blocking the cross link formation. Vancomycin inhibits
transglycosylase, so blocking further elongation of peptidoglycan chain.

2. A 67-year-old man recently diagnosed with Legionnaires' disease, started a treatment with a macrolide antibiotic. Which of the following is the primary site of action of the drug on bacterial cells?

The cytoplasmic membranes

The outer membrane

The porin channels

The peptidoglycan layer

The microsomes

The mitochondria

The ribosomes

Learning objective: identify the site of action of clarithromycin.
Answer: G
Macrolide antibiotics act by binding reversibly to the 50S subunit of the bacterial ribosome which is
therefore their primary cellular site of action.
A, B; C; D) Since macrolides act inside the bacterial cell, they must cross all the above mentioned
structures. These site are important for the pharmacokinetic of these drugs but they are not the site
of action of macrolides.
E, F) Macrolides do not affect mitochondria or ribosomes.

Explanation

Learning objective: identify the site of action of clarithromycin.
Answer: G
Macrolide antibiotics act by binding reversibly to the 50S subunit of the bacterial ribosome which is
therefore their primary cellular site of action.
A, B; C; D) Since macrolides act inside the bacterial cell, they must cross all the above mentioned
structures. These site are important for the pharmacokinetic of these drugs but they are not the site
of action of macrolides.
E, F) Macrolides do not affect mitochondria or ribosomes.

3. A 28-year-old man recently diagnosed with Rocky Mountains spotted fever started a treatment with doxycycline, two tablets daily. Which of the following is the primary site of action of this drug?

Bacterial cell walls

Bacterial cell membrane

30S subunit of bacterial ribosome

50S subunit of bacterial ribosome

Bacterial DNA

Learning objective: identify the site of action of tetracyclines.
Answer: C
Tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome and block the access of
aminoacyl-tRNA to the acceptor side of the mRNA ribosome complex. This prevent the addition of
amino acids to the growing peptide chain and therefore inhibits bacterial protein synthesis

Explanation

Learning objective: identify the site of action of tetracyclines.
Answer: C
Tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome and block the access of
aminoacyl-tRNA to the acceptor side of the mRNA ribosome complex. This prevent the addition of
amino acids to the growing peptide chain and therefore inhibits bacterial protein synthesis

4. The diagram below depicts a simplified pathway for the synthesis and breakdown of bacterial cell wall. Which of the steps shown in the pathway is specifically inhibited by beta-lactam antibiotics?

1

2

3

4

Learning objective: identify the specific step of the synthesis and breakdown of bacterial cell
wall which is inhibited by beta-lactam antibiotics.
Answer: C
Beta-lactam antibiotics inhibit cell wall synthesis by preventing cross-linking between the peptide
chains of the acetylmuramic acid. This linking is catalyzed by transpeptidase enzymes and beta
lactam antibiotics specifically inhibit these enzymes.
A) This step is inhibited by fosfomycin
B) This step is inhibited by vancomycin
D) This step is enhanced (not inhibited) by beta-lactam antibiotics and this action, together with the
inhibition of transpeptidase, contributes to the final bactericidal effect of these drugs.

Explanation

Learning objective: identify the specific step of the synthesis and breakdown of bacterial cell
wall which is inhibited by beta-lactam antibiotics.
Answer: C
Beta-lactam antibiotics inhibit cell wall synthesis by preventing cross-linking between the peptide
chains of the acetylmuramic acid. This linking is catalyzed by transpeptidase enzymes and beta
lactam antibiotics specifically inhibit these enzymes.
A) This step is inhibited by fosfomycin
B) This step is inhibited by vancomycin
D) This step is enhanced (not inhibited) by beta-lactam antibiotics and this action, together with the
inhibition of transpeptidase, contributes to the final bactericidal effect of these drugs.

5. A 34-year-old woman recently diagnosed with salpingitis due to Bacteroides fragilis started a treatment with a drug that is reduced by anaerobes to a highly reactive nitro radical anion able to damage bacterial DNA. Which of the following drugs did the patient most likely take?

Linezolid

Vancomycin

Ampicillin

Metronidazole

Tetracycline

Learning objective: explain the mechanism of action of metronidazole.
Answer: D
Metronidazole is an antibiotic active against most microaerophile and anaerobic bacteria and
anaerobic protozoa. These microorganisms , unlike their aerobic counterparts, contains electron
transport components, called ferredoxins, that can donate electrons to metronidazole. This donation
forms a highly reactive nitro radical anion that damages bacterial DNA. and. The ultimate effect is
bactericidal.

Explanation

Learning objective: explain the mechanism of action of metronidazole.
Answer: D
Metronidazole is an antibiotic active against most microaerophile and anaerobic bacteria and
anaerobic protozoa. These microorganisms , unlike their aerobic counterparts, contains electron
transport components, called ferredoxins, that can donate electrons to metronidazole. This donation
forms a highly reactive nitro radical anion that damages bacterial DNA. and. The ultimate effect is
bactericidal.

6. A 42-year-old man recently diagnosed with mycoplasmal pneumonia started a treatment with a fluoroquinolone, two tablet daily. Which of the following molecular actions most likely mediated the therapeutic effect of the drug in the patient's disease?

Inhibition of bacterial cell wall synthesis

Inhibition of relaxation of supercoiled bacterial DNA

Stimulation of synthesis of abnormal bacterial proteins

Inhibition of ergosterol synthesis in the bacterial cell membrane

Stimulation of bacterial DNA helicase

Stimulation of bacterial DNA-dependent RNA polymerase

Learning objective: explain the mechanism of action of fluoroquinolones
Answer: B
Fluoroquinolones Inhibit bacterial DNA synthesis by blocking the following enzymes:
1) Topoisomerase II (also called DNA gyrase). The blockade prevent the relaxation of supercoiled
DNA which is required for normal transcription (prevalent mechanism in gram-negative bacteria)
2) Topoisomerase IV. The blockade interferes with separation of replicated chromosomal DNA
during cell division (prevalent mechanism in gram-positive bacteria).

Explanation

Learning objective: explain the mechanism of action of fluoroquinolones
Answer: B
Fluoroquinolones Inhibit bacterial DNA synthesis by blocking the following enzymes:
1) Topoisomerase II (also called DNA gyrase). The blockade prevent the relaxation of supercoiled
DNA which is required for normal transcription (prevalent mechanism in gram-negative bacteria)
2) Topoisomerase IV. The blockade interferes with separation of replicated chromosomal DNA
during cell division (prevalent mechanism in gram-positive bacteria).

7. A 43-year-old woman recently diagnosed with urinary tract infection started a treatment with trimethoprim-sulfamethoxazole. The inhibition of which of the following molecular actions most likely mediated the therapeutic effect of the drug in the patient's disease?

Assembly of DNA by DNA-dependent RNA polymerase

Replication of bacterial RNA

Synthesis of bacterial purines and pyrimidines

Translocation of the newly synthesized peptidyl-tRNA

Access of the aminoacyl-tRNA to the acceptor site

Learning objective: explain the mechanism of action of sulfonamides
Answer: C
Sulfonamides inhibit folic acid synthesis which in turn inhibits the synthesis of tetrahydrofolate.
Since tetrahydrofolate is needed for the synthesis of purines and pyrimidines, the synthesis of these
molecules is blocked.
A, B, D, E) Sulfonamides have no effect on the function of already formed DNA or NRA

Explanation

Learning objective: explain the mechanism of action of sulfonamides
Answer: C
Sulfonamides inhibit folic acid synthesis which in turn inhibits the synthesis of tetrahydrofolate.
Since tetrahydrofolate is needed for the synthesis of purines and pyrimidines, the synthesis of these
molecules is blocked.
A, B, D, E) Sulfonamides have no effect on the function of already formed DNA or NRA

8. A 44-year-old man was admitted to the emergency room with the admitting diagnosis of bacterial sepsis. Further exams indicated that Enterococcus faecium was the offending pathogen and that the bacterium was vancomycin resistant. A treatment with linezolid was started. Which of the following was most likely the site of action of this drug?

The peptidoglycan layer

The outer membrane

The porin channels

The ribosomes

The microsomes

The mitochondria

Learning objective: identify the site of action of linezolid.
Answer: D
Linezolid binds to 50S ribosomal subunit at a site near to the 30 S ribosomal subunit so preventing
the formation of the initiation complex

Explanation

Learning objective: identify the site of action of linezolid.
Answer: D
Linezolid binds to 50S ribosomal subunit at a site near to the 30 S ribosomal subunit so preventing
the formation of the initiation complex

9. A 49-year-old woman, who was on vacation in the south of Italy, presented with fever, headache and a small, button like skin ulcer, 5 mm in diameter, with a black center. The diagnosis of Mediterranean spotted fever was made and the woman was prescribed doxycycline. Which of the following molecular actions most likely mediated the therapeutic effect of the drug in the patient 's disease?

Inhibition of DNA-dependent RNA polymerase

Blockade of the formation of ribosomal initiation complex

Blockade of transpeptidation reaction

Blockade of binding of aminoacyl-tRNA to bacterial ribosomes

Inhibition of transpeptidase enzymes

Learning objective: explain the mechanism of action of tetracyclines.
Answer: D
Mediterranean spotted fever (also called fiebre boutonneuse) is a disease caused by Rickettsia
conorii. Doxycycline is a tetracycline antibiotic that has became the drug of choice for most
rickettsial diseases, because of its efficacy, long half-life and very good oral bioavailability.
Tetracyclines bind reversibly to the 30s ribosomal subunit and block the access of aminoacyl-tRNA
to the acceptor side of the mRNA ribosome complex. This prevent the addition of amino acids to the
growing peptide chain and therefore inhibits bacterial protein synthesis

Explanation

Learning objective: explain the mechanism of action of tetracyclines.
Answer: D
Mediterranean spotted fever (also called fiebre boutonneuse) is a disease caused by Rickettsia
conorii. Doxycycline is a tetracycline antibiotic that has became the drug of choice for most
rickettsial diseases, because of its efficacy, long half-life and very good oral bioavailability.
Tetracyclines bind reversibly to the 30s ribosomal subunit and block the access of aminoacyl-tRNA
to the acceptor side of the mRNA ribosome complex. This prevent the addition of amino acids to the
growing peptide chain and therefore inhibits bacterial protein synthesis

10. A 33-year-old man was admitted to the hospital with the admitting diagnosis of bacterial pneumonia. Further exams indicated that pneumonia was due to Mycoplasma pneumonia and a treatment with a bacteriostatic antibiotic was started. The given antibiotic most likely belonged to which of the following classes?

Cephalosporins

Aminoglycosides

Macrolides

Carbapenems

Fluoroquinolones

Learning objective: list the main classes of bacteriostatic antibiotics.
Answer: C
Among the listed classes only macrolides are mainly bacteriostatic antibiotics. All beta-lactam drugs
(including cephalosporin and carbapenems) as well as aminoglycosides and fluoroquinolones are
bactericidal.

Explanation

Learning objective: list the main classes of bacteriostatic antibiotics.
Answer: C
Among the listed classes only macrolides are mainly bacteriostatic antibiotics. All beta-lactam drugs
(including cephalosporin and carbapenems) as well as aminoglycosides and fluoroquinolones are
bactericidal.

11. A 31-year-old woman, diagnosed with acute cystitis, started a treatment with trimethoprim-sulfamethoxazole combination. Which of the following groups of steps shown in the pathway below was most likely inhibited by that treatment?

1, 2, 3

2, 4, 5

1, 2, 4

3, 4, 5

1, 3, 5

Learning objective: explain the mechanism of action of trimethoprim-sulfamethoxazole
combination.
Answer: A
By inhibiting dihydropteroate synthase, sulfonamides inhibit the formation of folate. By inhibiting
dihydrofolate reductase, trimethoprim inhibits the formation of dihydrofolate and tetrahydrofolate.
Inhibition of these consecutive steps in the formation of tetrahydrofolate constitute a sequential
blockade and results in antibacterial synergy.
B, C, D, E) The synthesis of DNA and RNA from already formed tetrahydrofolate are not inhibited by
trimethoprim sulfamethoxazole.

Explanation

Learning objective: explain the mechanism of action of trimethoprim-sulfamethoxazole
combination.
Answer: A
By inhibiting dihydropteroate synthase, sulfonamides inhibit the formation of folate. By inhibiting
dihydrofolate reductase, trimethoprim inhibits the formation of dihydrofolate and tetrahydrofolate.
Inhibition of these consecutive steps in the formation of tetrahydrofolate constitute a sequential
blockade and results in antibacterial synergy.
B, C, D, E) The synthesis of DNA and RNA from already formed tetrahydrofolate are not inhibited by
trimethoprim sulfamethoxazole.

12. A 32-year-old woman on a vacation trip in east Asia was diagnosed with acute conjunctivitis. A topical treatment with chloramphenicol was able to heal completely the disease. Which of the following molecular actions most likely mediated the therapeutic efficacy of the drug in the patient's disease?

Inhibition of cross linking of linear peptidoglycan chains

Blockade of transpeptidation reaction of protein synthesis

Inhibition of relaxation of supercoiled bacterial DNA

Inhibition of ergosterol synthesis in the bacterial cell membrane

Misreading of the mRNA template in the ribosomal subunit

Learning objective: explain the mechanism of action of chloramphenicol
Answer: B
Chloramphenicol enters the cell by facilitated diffusion and binds reversibly with the 50s ribosomal
subunit. In this site it prevents binding of the amino acid containing end of the aminoacyl tRNA to
the acceptor site of the 50S ribosomal subunit. Thus the peptide at the donor site cannot be
transferred to its amino acid acceptor, that is the transpeptidation reaction cannot occur. This
reaction is catalyzed by peptidyl transferase that is therefore indirectly inhibited by chloramphenicol.

Explanation

Learning objective: explain the mechanism of action of chloramphenicol
Answer: B
Chloramphenicol enters the cell by facilitated diffusion and binds reversibly with the 50s ribosomal
subunit. In this site it prevents binding of the amino acid containing end of the aminoacyl tRNA to
the acceptor site of the 50S ribosomal subunit. Thus the peptide at the donor site cannot be
transferred to its amino acid acceptor, that is the transpeptidation reaction cannot occur. This
reaction is catalyzed by peptidyl transferase that is therefore indirectly inhibited by chloramphenicol.

13. A 60-year-old man was recently diagnosed with osteomyelitis due to staphylococci that turned out to be vancomycin resistant. The patient started a therapy with two antibiotics of the streptogramin group. Which of the following is the primary site of action of these antibiotics?

The ribosomes

The outer membrane

The porin channels

The peptidoglycan layer

The microsomes

The mitochondria

The cytoplasmic membranes

Learning objective: identify the site of action of quinupristin and dalfopristin.
Answer: A
Quinupristin and dalfopristin are antibiotics of the streptogramin group. They bind to tow separate
sites on the 50S bacterial ribosome, forming a stable ternary complex. Thus they synergistically
interrupt protein synthesis.

Explanation

Learning objective: identify the site of action of quinupristin and dalfopristin.
Answer: A
Quinupristin and dalfopristin are antibiotics of the streptogramin group. They bind to tow separate
sites on the 50S bacterial ribosome, forming a stable ternary complex. Thus they synergistically
interrupt protein synthesis.

14. A 48-year-old man recently diagnosed with campylobacter diarrhea started a treatment with an antibiotic that blocks the transfer of peptidyl tRNA from the acceptor site to the peptidyl site of the bacterial ribosome. The given antibiotic most likely belonged to which of the following classes?

Sulfonamides

Fluoroquinolones

Macrolides

Beta-lactam drugs

Aminoglycosides

Learning objective: explain the mechanism of action of macrolides
Answer: C.
Macrolide and lincosamides antibiotics block the translocation reaction, i.e. the transfer of peptidyl
tRNA from the acceptor site to the peptidyl site of the bacterial ribosome. The ultimate effect is
mainly bacteriostatic.

Explanation

Learning objective: explain the mechanism of action of macrolides
Answer: C.
Macrolide and lincosamides antibiotics block the translocation reaction, i.e. the transfer of peptidyl
tRNA from the acceptor site to the peptidyl site of the bacterial ribosome. The ultimate effect is
mainly bacteriostatic.

15. A 34-year-old man recently diagnosed with streptococcal pharyngitis started a treatment with amoxicillin, two tablets daily. Which of the following statements best explains a prominent feature of the antibacterial action of this beta-lactam antibiotic?

It can inhibit bacterial growth but cannot kill bacteria

It increases with increasing concentration of the drug

It exhibits a long post antibiotic effect

It continues as long as the concentration is greater that MBC

It involves the inhibition of bacterial autolysins

Learning objective: describe the antibacterial action of beta-lactam antibiotics.
Answer: D
Beta-lactam antibiotic exert aa bactericidal effect which is time dependent, that is the killing
continues as long as the serum concentration of the drug is grater than the minimum bactericidal
concentration ()MBC).
A) All beta-lactam antibiotics are mainly bactericidal.
B) The antibacterial action of beta-lactam antibiotics is not concentration dependent.
C) Among beta-lactam antibiotics only carbapenems haves a postantibiotic effect.
E) The antibacterial action involves an activation, not an inhibition, of bacterial autolysins which are
able to destroy the bacterial cell wall.

Explanation

Learning objective: describe the antibacterial action of beta-lactam antibiotics.
Answer: D
Beta-lactam antibiotic exert aa bactericidal effect which is time dependent, that is the killing
continues as long as the serum concentration of the drug is grater than the minimum bactericidal
concentration ()MBC).
A) All beta-lactam antibiotics are mainly bactericidal.
B) The antibacterial action of beta-lactam antibiotics is not concentration dependent.
C) Among beta-lactam antibiotics only carbapenems haves a postantibiotic effect.
E) The antibacterial action involves an activation, not an inhibition, of bacterial autolysins which are
able to destroy the bacterial cell wall.