A Klebsiella pneumoniae strain isolated from a urinary tract infection carries the plasmid‑mediated mcr-1 gene. (a) Explain how the mcr-1 gene confers resistance to colistin. (b) Suggest an alternative oral antibiotic that would likely be effective against this strain and justify your choice.
Answer
mcr‑1 encodes a phosphoethanolamine transferase that modifies lipid A, reducing colistin binding; fosfomycin, which inhibits MurA, is an effective oral antibiotic.
Step-by-step solution
- mcr‑1 encodes a phosphoethanolamine transferase enzyme.
- The enzyme adds phosphoethanolamine to the lipid A moiety of LPS.
- This reduces the negative charge on the outer membrane, decreasing affinity of the cationic drug colistin.
- Colistin can no longer bind and disrupt the membrane, conferring resistance.
- Fosfomycin inhibits MurA, blocking peptidoglycan synthesis.
- Its mechanism does not involve the outer membrane, so mcr‑1 modification does not affect it.
- Therefore fosfomycin is an effective oral choice against this strain.
Common mistake: Believing mcr-1 inactivates colistin by hydrolysis
Concept tested: Plasmid‑mediated colistin resistance
Published · How this solution was prepared and checked
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