A 19-year-old man comes to the office with an ulcer on his penis. The patient first noticed the lesion 3 days ago. His temperature is 37.1 C (98.8 F). Physical examination shows an indurated and painless ulcer near the glans penis, with no surrounding erythema and no inguinal lymphadenopathy. The patient is a college student. He has no significant past medical history and takes no medications. He has no known drug allergies. The first-line treatment for this patient has structural similarities with which of the following?

Question

A 19-year-old man comes to the office with an ulcer on his penis.  The patient first noticed the lesion 3 days ago.  His temperature is 37.1 C (98.8 F).  Physical examination shows an indurated and painless ulcer near the glans penis, with no surrounding erythema and no inguinal lymphadenopathy.  The patient is a college student.  He has no significant past medical history and takes no medications.  He has no known drug allergies.  The first-line treatment for this patient has structural similarities with which of the following?

Quizplus · Accepted Answer

This patient likely has a chancre due to primary syphilis, a sexually transmitted infection caused by the spirochete Treponema pallidum. Spirochetes are universally sensitive to penicillin because they are all gram-negative organisms with a peptidoglycan cell wall. Penicillins work by covalently binding to and inhibiting transpeptidase. This enzyme catalyzes the final cross-linking step in peptidoglycan cell wall formation: the joining of the amino acid in the third position of a peptidoglycan molecule to the terminal D-alanine-D-alanine of another peptidoglycan molecule. The structural similarity of penicillins to D-alanine-D-alanine likely facilitates their binding to transpeptidase. When transpeptidase is inhibited, cell wall synthesis ceases and cell wall degradation by bacterial autolysins proceeds unchecked. The weakened cell wall integrity causes osmotic lysis of the bacterium. Vancomycin, a glycopeptide antibiotic, directly binds to the D-alanine-D-alanine residues, preventing the incorporation of new subunits into the cell wall. Vancomycin acts at an earlier stage of cell wall formation than do the penicillins. (Choices B and D) D-glutamic acid-D-glutamic acid and L-alanine-D-glutamine are not sequences targeted by transpeptidase. Penicillin is not a structural analog of either molecule. (Choice C) Sulfonamide antibiotics are antimetabolites that compete with para-aminobenzoic acid for incorporation into folic acid. Trimethoprim blocks another step in folic acid synthesis by inhibiting the enzyme dihydrofolate reductase. (Choices E and F) Peptidoglycan precursor molecules consist of a disaccharide composed of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc). Educational objective: Penicillins, structurally similar to D-alanine-D-alanine, inhibit transpeptidase by binding covalently to its active site. The result is failed synthesis of the bacterial peptidoglycan cell wall.

A 19-Year-Old Man Comes to the Office with an Ulcer