A patient with hospital-acquired pneumonia grows pan-drug-resistant (PDR) Acinetobacter baumannii from BAL culture. The only remaining option is colistin (polymyxin E). The mechanism of colistin resistance in Acinetobacter most commonly involves:

• A Plasmid-mediated MCR-1 gene encoding phosphoethanolamine transferase modifying lipid A in Acinetobacter
• B Efflux pump overexpression (AdeABC) pumping out colistin from the outer membrane
• C OmpA outer membrane protein mutation reducing colistin binding sites on the bacterial surface
• D Modification of lipid A by addition of phosphoethanolamine (via pmrC/eptA) or 4-amino-4-deoxy-L-arabinose, reducing cationic charge repulsion ✓

Explanation

Colistin disrupts Gram-negative bacterial outer membranes by binding to the negatively charged lipopolysaccharide (LPS) lipid A moiety through electrostatic interactions. Colistin resistance in Acinetobacter baumannii most commonly results from chromosomal mutations in pmrA/pmrB (two-component regulatory system) and lpxA/lpxC/lpxD (lipid A biosynthesis genes), leading to lipid A modification by addition of phosphoethanolamine (via eptA/pmrC) — this addition reduces the negative charge of LPS, decreasing electrostatic attraction for colistin. Complete loss of LPS (lpxA/B/D mutations) is another mechanism unique to Acinetobacter. MCR-1 is a plasmid-mediated mechanism primarily in Enterobacteriaceae (E. coli, Klebsiella), not predominantly in Acinetobacter. AdeABC efflux pumps do not effectively export polymyxins.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.