Table 1.

Mechanisms of polymyxin resistance.

Bacteria	Polymyxin Mechanisms of Resistance	References
Klebsiella pneumoniae	•Expression of phoP/phoQ and pmrA/pmrB •Point mutations within pmrA/B upregulation of the operon arnBCADTEF and pmrC •Production of capsular polysaccharide (CPS) inhibits binding of polymyxins to lipid A •KpnEF and AcrAB encodes efflux pumps •Mutations in KpnEF and AcrAB	[[82], [92], [93]]
Acinetobacter baumannii	•Mutations in pmrA and pmrB genes •Upregulation of the pmrCAB operon resulting in transcription of pmrC encoding EptA •Mutations in lpxA, lpxB or lpxC involved in lipid A biosynthesis pathway	[92]
Pseudomonas aeruginosa	•Five Two-Component Systems (PmrAB, PhoPQ, ParRS, ColRS and CprRS) in P. aeruginosa influence L-Ara4N modifications on the lipid A •Outer membrane protein (OprH or H1) of P. aeruginosa binds to the phosphate groups on the LPS hindering polymyxin binding	[[82], [93]]
Enterobacter	•Mutation in phoP •Inactivation of the mgrB gene •Ecr transmembrane protein acts on the phoPQ component system to activate the pbgP operon leading to increase in LPS modification •Heteroresistance to polymyxin	[[94], [95], [96]]
E. coli	•Modification of the PmrAB •arnT gene encode a glycosyltransferase catalysing the transfer of L-Ara4N to a phosphate group of lipid A •Polymyxin efflux activity involving marRAB, sap AcrAB-TolC efflux genes	[[74], [97], [98], [99]]
Proteus	•Proteus spp. exhibit natural resistance to polymyxins due to the presence of l-arabinose-4-amine attached to the Kdo (3-deoxy-d-manno-oct-2-ulosonic acid) residue on the lipid A moiety of the LPS •EptC gene involved in modification of the LPS with PEtN addition	[[100], [101]]
Citrobacter	•Mutations in the TCS sensor kinase pmrB •MgrR negatively regulates eptB to mediate the modification of the outer Kdo residues of LPS with PEtN.	[[82], [95]]