Table 1.
Strategies employed by bacteria for achieving resistance to colistin.
| Genes Involved | Resistance Mechanism | Bacteria | Ref |
|---|---|---|---|
| LPS modifications | |||
| arnBCADTEF operon and pmrE | Modification of the lipid A with aminoarabinose |
Salmonella enterica, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Proteeae bacteria, Serratia marcescens and P. aeruginosa |
[38,39,40,41,42,43,44,45] |
| crrB (crrC) | The regulatory systems of two-component PhoP-PhoQ and PmrA-PmrB (response regulator/sensor kinase) | K. pneumoniae CG43 | [25,46] |
| pmrAB, pmrD, phoPQ, parRS, mcr | L-Ara4N and PEtn modification of lipid A | E. coli, Salmonella enterica, P. aeruginosa | [25,40,47] |
| ParR/ParS, ColR/ColS and CprR/CprS | LPS modification with aminoarabinose |
P. aeruginosa | [11,21] |
| mgrB | Structural modifications of the lipid A subunit | K. pneumonia | [22,23] |
| lpxACD, lptD | Loss of LPS | Acinetobacter baumannii | [24,48] |
| pmrC | Modification of the lipid A phosphoethanolamine |
S. enterica, K. pneumoniae, E. coli and Acinetobacter baumannii |
[38,49] |
| mcr-1 to mcr-8 | Inactivation of lipid A biosynthesis | E. Coli and K. pneumonia | [11,50] |
| Pag, PagL, LpxM and LpxO | Modifications on cell surface regarding electrostatic repulsion of colistin Decreasing membrane fluidity/permeability |
K. pneumoniae, E. coli, S. enterica and Legionella pneumophila | [25,51] |
| Bmul_2133/Bmul_2134 | phosphorylation, dephosphorylation, glycylation and glucosylation of lipid A | Burkholderia multivorans | [28,52] |
| Repulsion mechanism | |||
| dlt-ABCD, graXSR, dra/dlt, liaSR and CiaR operons | Adding D-alanine (D-Ala) to teichoic acids, thereby increasing net positive charge | Staphylococcus aureus, Bordetella pertussis, Streptococcus gordonii, Listeria monocytogenes and Group B Streptococcus | [53,54] |
| Membrane remodelling | |||
| siaD, cps operon, ompA, kpnEF, phoPQ and rcs | Loss of polymyxin target and capsule polysaccharide (CPS) overproduction | Neisseria meningitidis, K. pneumoniae and S. enterica | [40] |
| virB, suhB Bc, bvrRS, epsC-N, cgh, vacJ, waaL, rfbA, ompW, micF, pilMNOPQ operon, parRS, rsmA, bveA, ydeI (omdA), ompD (nmpC), ygiW (visP), ompF, rcs | Altered membrane composition | Brucella ovis, S. enterica, Brucella melitensis, Burkholderia cenocepacia, Vibrio cholerae, Brucella abortus, K. pneumoniae, P. aeruginosa, N. meningitidis and Brucella melitensis | [29,40] |
| cas9, tracrRNA, scaRNA, Lol, TolQRA | Altered membrane integrity | Stenotrophomonas maltophilia, Vibrio fischeri, B. cenocepacia, E. coli, P. aeruginosa, Salmonella Typhimurium, Campylobacter jejuni and Haemophilus influenzae | |
| spgM, pgm, hldA, hldD, oprH, cj1136, waaF, lgtF, galT, cstII, galU | Lipooligosaccharide (LOS) and LPS modification | ||
| Modifications to OM porins and overexpression of efflux pump systems | |||
| OmpU, OmpA and PorB | Mutations in outer membrane porins | N. meningitidis and V. cholerae | [32] |
| MtrC –MtrD –MtrE, RosAB, AcrAB–TolC | An important role in tolerance toward polymyxin B | E. coli | [33] |
| NorM, KpnEF and VexAB | Neisseria gonorrhoeae | ||
| dedA | playing an important role in membrane homeostasis | E. coli | [34,35,36,37] |