A novel antimicrobial agent that inhibits bacterial glycosyltransferase enzyme is developed. Bacteria grown in a medium containing this antibiotic become spherical, cease to grow, and subsequently lyse. So that the activity of this antibiotic against various bacteria can be determined, disks enriched with the drug are placed on agar plates containing bacterial colonies. The plates are incubated alongside control plates with the same organisms but no antimicrobial disks. The control plates all show organism growth. In the plates with the diffusion disks, resistance to the drug is determined by measuring the zone of complete growth inhibition around the disk. Which of the following bacteria is most likely to be resistant to this drug?

Question

A novel antimicrobial agent that inhibits bacterial glycosyltransferase enzyme is developed.  Bacteria grown in a medium containing this antibiotic become spherical, cease to grow, and subsequently lyse.  So that the activity of this antibiotic against various bacteria can be determined, disks enriched with the drug are placed on agar plates containing bacterial colonies.  The plates are incubated alongside control plates with the same organisms but no antimicrobial disks.  The control plates all show organism growth.  In the plates with the diffusion disks, resistance to the drug is determined by measuring the zone of complete growth inhibition around the disk.  Which of the following bacteria is most likely to be resistant to this drug?

Quizplus · Accepted Answer

Peptidoglycan is the main component of the bacterial wall in both gram-positive and gram-negative organisms. It is composed of a linear glycan chain of 2 alternating sugars, N-acetylglucosamine and N-acetylmuramic acid, that are cross-linked by short peptides, thereby forming a rigid matrix. The enzyme glycosyltransferase is a crucial component of peptidoglycan synthesis; it adds glycan molecules to the growing peptidoglycan chain. Inhibition of this enzyme would result in gaps in the bacterial cell wall, with subsequent loss of bacterial shape and cell lysis from osmotic stress. Although most bacteria have a cell wall composed of peptidoglycan, organisms from the Mycoplasma genus (eg, Ureaplasma urealyticum, M hominis) completely lack a cell wall. These pathogens are separated from the environment by a single phospholipid bilayer membrane composed primarily of cholesterol (similar to human cells). Therefore, antibacterial agents that target the cell wall, including penicillins, cephalosporins, carbapenems, vancomycin, and the drug described in this study, would be ineffective. Mycoplasma is treated primarily by medications that inhibit bacterial ribosomal function such as macrolides and tetracyclines. (Choice A) Actinomyces israelii is a gram-positive, fungus-like bacterium that has a thick peptidoglycan cell wall. Therefore, it is likely to be inhibited by the drug described in this study. It can be effectively treated with penicillin. (Choices B and E) Borrelia burgdorferi is the spirochete that causes Lyme disease. Pasteurella multocida is a gram-negative organism that is well-known for causing wound infections following cat bites. Because these organisms have peptidoglycan cell walls, they would likely be inhibited by a drug that blocks glycosyltransferase. (Choice C) Helicobacter pylori, a gram-negative helical organism with a cell wall, is closely related to the Campylobacter genus. The recommended treatment regimen includes a proton pump inhibitor (eg, omeprazole) combined with clarithromycin and amoxicillin, with or without bismuth (triple or quadruple therapy). Educational objective: All organisms in the Mycoplasma genus, including Ureaplasma urealyticum, lack peptidoglycan cell walls and are therefore resistant to agents that target the cell wall such as penicillins, cephalosporins, carbapenems, and vancomycin. Mycoplasma infections can be treated with antiribosomal agents (eg, tetracyclines, macrolides).

A Novel Antimicrobial Agent That Inhibits Bacterial Glycosyltransferase Enzyme Is