Pseudomonas exotoxin inhibits protein synthesis by inhibiting –
Pseudomonas aeruginosa is a common pathogen, especially in immunocompromised patients or those with cystic fibrosis. Their exotoxins include Exotoxin A, which is a major virulence factor. From what I remember, Exotoxin A works by inhibiting protein synthesis. But how exactly does it do that?
Protein synthesis involves several steps: initiation, elongation, and termination. The key enzymes here would be the elongation factors. In eukaryotes, EF-2 (elongation factor 2) is crucial for the translocation step during elongation. If Exotoxin A inhibits EF-2, that would block the movement of the ribosome along the mRNA, stopping protein synthesis.
Wait, but some toxins affect prokaryotic systems. For example, diphtheria toxin inhibits EF-2 in prokaryotes. However, Exotoxin A targets eukaryotic cells. So, it's more likely that it inhibits eukaryotic EF-2. Let me confirm that. Yes, Exotoxin A ADP-ribosylates EF-2 in eukaryotic cells, which inactivates it. This prevents the ribosome from translocating, thus halting protein synthesis.
Looking at the options, the correct answer would be the one mentioning EF-2. The other options might include things like RNA polymerase, ribosome subunits, or other factors like EF-1. For example, if an option says "RNA polymerase," that's incorrect because the toxin doesn't affect transcription but translation. Another option might be about inhibiting ribosome assembly, but Exotoxin A specifically targets EF-2 during elongation.
Clinical pearl: Remember that Exotoxin A from Pseudomonas is similar to diphtheria toxin in mechanism but acts on eukaryotic EF-2. This is a high-yield point for exams like NEET or USMLE. Also, knowing that toxins from different bacteria have distinct targets can help differentiate their mechanisms.
**Core Concept**
Pseudomonas aeruginosa exotoxin A inhibits protein synthesis by ADP-ribosylating elongation factor 2 (EF-2), a key component of the eukaryotic translation elongation machinery. This prevents ribosomal translocation during protein synthesis, halting translation.
**Why the Correct Answer is Right**
Exotoxin A catalyzes the transfer of ADP-ribose from NAD to a specific diphthamide residue in EF-2. This modification inactivates EF-2, which is essential for the ribosome to move along the mRNA during elongation. Without functional EF-2, the ribosome cannot translocate, leading to global inhibition of protein synthesis in eukaryotic cells. This mechanism is similar to diphtheria toxin but targets eukaryotic EF-2 instead of prokaryotic EF-2.
**Why Each Wrong Option is Incorrect**
**Option A:** Inhibits RNA polymerase β Incorrect. Exotoxin A does not affect transcription (RNA synthesis