Colistin Resistance
One-Sentence Definition
Colistin (polymyxin E) resistance is reduced activity of last-line cationic peptide antibiotics against Gram-negatives, mediated mainly by LPS lipid A modifications (chromosomal regulatory mutations or mobile mcr phosphoethanolamine transferases).
Simple Explanation
Colistin punches holes in the outer membrane by sticking to bacterial endotoxin. Resistant bugs chemically remodel that surface charge so colistin can no longer bind well — sometimes via a plasmid gene that can jump between species.
Detailed Scientific Explanation
| Mechanism class | Examples | Mobility |
|---|---|---|
| Chromosomal regulatory | PhoPQ, PmrAB, MgrB disruption (Klebsiella) → L-Ara4N / pEtN on lipid A | Vertical / mutational |
| Mobile mcr | mcr-1… phosphoethanolamine transferases | Plasmid (Horizontal Gene Transfer) |
| Intrinsic | Proteus, Serratia, Burkholderia — naturally less susceptible | N/A |
Detection challenges:
- Colistin MIC methods finicky (broth microdilution reference; agar dilution/other methods limited)
- Heteroresistance common
- Molecular: mcr PCR / WGS; chromosomal lesions need careful interpretation (Genotype to Phenotype Prediction)
Mechanism
Positive charge of polymyxin attracted to negatively charged lipid A → membrane disruption. Adding positively charged moieties (Ara4N, pEtN) reduces binding → survival.
Clinical Importance
- Used for XDR CRE / MDR Acinetobacter / Pseudomonas when few options remain — nephro/neurotoxicity limits use
- Resistance rises under selective pressure; infection control + stewardship essential
- Mobile mcr is a One Health red flag (livestock ↔ human interface) (One Health)
Research Importance
- Global mcr plasmid maps; combination therapies; new polymyxin derivatives
- Bacterial GWAS / ML features for polymyxin MIC (Machine Learning for AMR Prediction)
Diagnostic Relevance
- Reference BMD for MIC; EUCAST/CLSI rules evolve
- Report mcr when found — epidemiologic importance even if local therapy differs
- WGS surveillance pipelines flag mcr + MgrB/PhoPQ/PmrAB hits (AMR Gene Databases)
AMR Relevance
Last-line Gram-negative AMR. Often stacked on CRE plasmids already carrying ESBL / Carbapenemases genes — truly extensively drug-resistant phenotypes.
Related Organisms
Related Methods
Related MOCs
Learning Aids
Clinical Example
Example
Case: NDM-producing E. coli; colistin MIC 4 µg/mL; WGS shows mcr-1 on an IncX4 plasmid.
Question: Chromosomal PhoPQ mutation or mobile resistance?
Answer: Mobile mcr-1 — IPC and One Health implications beyond this patient; seek alternative active agents.
Active Recall Questions
- What LPS change reduces colistin binding?
- Why is mcr especially concerning compared with MgrB loss?
- Which AST method is the reference for colistin MIC?