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Review

Lantibiotic Resistance

Lorraine A. Draper, Paul D. Cotter, Colin Hill, R. Paul Ross
Lorraine A. Draper
aSchool of Microbiology, University College Cork, Cork, Ireland
bAlimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
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Paul D. Cotter
bAlimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
cTeagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland
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Colin Hill
aSchool of Microbiology, University College Cork, Cork, Ireland
bAlimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
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R. Paul Ross
aSchool of Microbiology, University College Cork, Cork, Ireland
bAlimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
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DOI: 10.1128/MMBR.00051-14
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    FIG 1

    Mechanisms of lantibiotic resistance which relate to the cell wall and membrane. (A) d-Alanylation of lipoteichoic acids (LTA) and wall teichoic acids (WTA) by the dltABCD operon, which confers a positive charge. (B) Changes in phospholipid composition. (C) Changes in membrane fatty acid composition. (D) Cell wall thickening. (E) Lysine esterification of one of the two hydroxyl groups of phosphatidylglycerol (PG) by Mprf. (F) Gram-negative outer cell membrane containing lipopolysaccharide (LPS).

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    FIG 2

    Two main types of two-component systems (TCSs) are responsible for lantibiotic resistance: the Bce-like TCSs (A) and the Lia-like TCSs (B). The presence of antimicrobials, such as lantibiotics, or the cell damage incurred as a result of their presence causes these TCSs to mediate the transcription of genes whose products confer a resistance phenotype.

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    FIG 3

    In S. aureus, three main TCSs are responsible for lantibiotic/antimicrobial resistance. These include two Bce-like TCSs, BraRS and GraRS, and an Lia-like TCS, VraSR. A coordinated resistance effort results from the actions of these TCSs, causing upregulation of genes whose products alter the composition of the cell wall and membrane and also of genes encoding ABC transporters which expel antimicrobials from the cell.

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  • TABLE 1

    Summary of lantibiotic resistance methodsa

    Resistance mechanism and relevant protein(s) or operonSpeciesRegulator(s)Lantibiotic resistance(s)
    Cell wall/membrane-altering mechanisms
        MprfS. aureus, L. monocytogenesVirRS/GraRSNisin, gallidermin
        DltAStreptococcus spp., Staphylococcus spp., L. monocytogenes, L. lactis, B. subtilis, C. difficileVirRS/sigma factorsNisin, gallidermin
        gal operonL. lactisNisin
        Penicillin-binding proteinL. monocytogenes, L. lactis, S. aureusLiaRS, LisRK, VraSR, sigma factorsNisin
        Lipid composition, including the fab operonL. monocytogenes, L. lactisNisin
    Miscellaneous resistance mechanisms
        Nisin resistance protein*L. lactis, Corynebacterium spp., Leuconostoc spp., Enterococcus spp., Streptococcus spp.Nisin
        Nisinase*S. thermophilus, L. plantarum, C. botulinum, L. lactis, E. faecalis, S. aureus, Bacillus spp.Nisin, subtilin
        GadL. monocytogenesNisin
        NsrXS. mutansNsrRSNisin
        arc operonL. lactisNisin
        PurRS. aureusNisin
        IreK-IreP-IreBE. faecalisNisin
        Sigma factorsL. monocytogenes, B. subtilisNisin, sublancin, mersacidin, subtilin gallidermin
        VraFGS. aureusGraXRSNisin, nukacin ISK-1
        CprABCC. difficileCprRKNisin, gallidermin
        AnrABL. monocytogenesVirRSNisin
        VraDES. aureusBraRS, VraSRNisin
        YsaBCL. lactisLlrG/KinGNisin
        BraDES. aureusBraRSNisin
        Lmo1746-Lmo1747L. monocytogenesVirRS, LiaRSNisin
        BceABB. subtilisBceRSActagardine, mersacidin
        PsdABB. subtilisPsdRSNisin, gallidermin, subtilin, actagardine
        Sp0912-Sp0913S. pneumoniaeRr01-Hk01Nisin
        LctFEGS. mutansLcrRSNukacin ISK-1, lacticin 481
        NsrFPCorynebacterium spp., Leuconostoc spp., Enterococcus spp., Streptococcus spp.NsrRKNisin
        TelAL. monocytogenesLiaRSNisin, gallidermin
        EfdFE*E. faeciumLacticin 3147
        SpiFEG*S. infantariusSpiRR′K?Nisin
    Two-component systems
        TC09, TC12L. caseiNisin
        GrsRSS. aureusNisin, nukacin ISK-1
        BraRSS. aureusNisin, nukacin ISK-1
        PsdRSB. subtilisNisin, gallidermin, subtilin, actagardine
        LlrG/KinGL. lactisNisin
        ApsRSS. epidermidisNisin
        BceRSBacillus spp.Actagardine, mersacidin
        LiaRSBacillus spp., Streptococcus spp., L. monocytogenesNisin
        NsrRSS. mutansNisin, lacticin 481, nukacin ISK-1
        LcrRSS. mutansNukacin ISK-1, lacticin 481
        VraSRS. aureusNisin, mersacidin, nukacin ISK-1
        LisRKL. monocytogenesNisin
        CesSRL. lactisNisin, plantaricin C
        VirRSL. monocytogenesNisin
        CprRKC. difficileNisin, gallidermin, subtilin, mutacin 1140, cinnamycin
    • ↵a The table lists the strains in which lantibiotic resistance has been observed and the lantibiotics to which this resistance is targeted. Not included in the table are the general resistance mechanism inferred by the Gram-negative cell wall and that of spore or biofilm formation. Lantibiotic-specific resistance methods are indicated with asterisks.

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Lantibiotic Resistance
Lorraine A. Draper, Paul D. Cotter, Colin Hill, R. Paul Ross
Microbiology and Molecular Biology Reviews Mar 2015, 79 (2) 171-191; DOI: 10.1128/MMBR.00051-14

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Lantibiotic Resistance
Lorraine A. Draper, Paul D. Cotter, Colin Hill, R. Paul Ross
Microbiology and Molecular Biology Reviews Mar 2015, 79 (2) 171-191; DOI: 10.1128/MMBR.00051-14
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  • Top
  • Article
    • SUMMARY
    • INTRODUCTION
    • MODE OF ACTION
    • ROLE OF CELL WALL MODIFICATIONS IN RESISTANCE
    • CELL MEMBRANE MODIFICATIONS
    • TWO-COMPONENT SYSTEMS ASSOCIATED WITH LANTIBIOTIC RESISTANCE
    • OTHER RESISTANCE ELEMENTS
    • CONCLUSIONS
    • ACKNOWLEDGMENT
    • REFERENCES
    • Author Bios
  • Figures & Data
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