Selective toxicity of ribosome-targeting antibiotics
Antibiotics that block protein synthesis spare human cells because bacterial ribosomes differ in structure from the ribosomes in the cytoplasm of human cells, though selectivity is relative.
Remember
Protein synthesis inhibitors work at the bacterial ribosome, which differs in structure from the human cytoplasmic ribosome, but the ribosomes inside human mitochondria resemble bacterial ones, so selectivity is relative, not absolute.
A ribosome is the cell's protein-building machine. It reads messenger RNA (mRNA, the working copy of a gene) and joins amino acids into a protein. Bacterial ribosomes and human ribosomes are different enough for selective targeting.
Bacteria have 70S ribosomes, built from a 30S subunit and a 50S subunit (the two parts that together make the whole ribosome). Human cells have 80S ribosomes in their cytoplasm. The S stands for the Svedberg unit, a measure from how a particle settles when it is spun, so the numbers do not simply add up: 30S and 50S together make 70S.
Aminoglycosides and tetracyclines bind the 30S subunit, whereas macrolides bind the 50S subunit; these are antibiotics that inhibit protein synthesis at the ribosome. Bound to the bacterial ribosome, they stop protein synthesis there, largely sparing human cytoplasmic ribosomes. This is selective toxicity: the microbe has the target and the host either lacks it or has it in a clearly different form.
The selectivity is relative rather than total. Human mitochondria have ribosomes of their own that resemble bacterial ones, so an antibiotic such as chloramphenicol, which targets ribosomes, can also suppress protein synthesis in human mitochondria.
Key facts
- Bacterial ribosome
- 70S, built from a 30S subunit and a 50S subunit.
- Human cytoplasmic ribosome
- 80S, made of 40S and 60S subunits.
- Aminoglycosides and tetracyclines
- bind the 30S subunit.
- Macrolides
- bind the 50S subunit.
- Svedberg numbers
- they do not simply add up, since 30S and 50S together make 70S.
- Limit of selectivity
- human mitochondria have ribosomes that resemble bacterial ones, so selectivity is relative.
Exam traps
- The 80S ribosome, with 40S and 60S subunits, is the human type and not the bacterial type; bacteria have the 70S ribosome, made of 30S and 50S subunits.
- A larger bacterial ribosome is the wrong way round: the bacterial 70S ribosome is smaller and simpler than the human cytoplasmic 80S ribosome, and size is not the reason anyway.
- Human mitochondria carry ribosomes of their own that resemble bacterial ones, which is why selectivity is relative and an antibiotic such as chloramphenicol can suppress mitochondrial protein synthesis.
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