199
Views
19
CrossRef citations to date
0
Altmetric
Review

Therapeutic compounds targeting Lipid II for antibacterial purposes

&
Pages 2613-2625 | Published online: 23 Aug 2019

References

  • Breukink E, de Kruijff B. Lipid II as a target for antibiotics. Nat Rev Drug Discov. 2006;5(4):321–332. doi:10.1038/nrd200416531990
  • van Heijenoort J. Lipid intermediates in the biosynthesis of bacterial peptidoglycan. Microbiol Mol Biol Rev. 2007;71(4):620–635. doi:10.1128/MMBR.00016-0718063720
  • de Kruijff B, van Dam V, Breukink E. Lipid II: a central component in bacterial cell wall synthesis and a target for antibiotics. Prostaglandins Leukot Essent Fatty Acids. 2008;79(3–5):117–121. doi:10.1016/j.plefa.2008.09.02019008088
  • Hsu ST, Breukink E, Tischenko E, et al. The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics. Nat Struct Mol Biol. 2004;11(10):963–967. doi:10.1038/nsmb83015361862
  • Okesola AO. Community-acquired methicillin-resistant Staphylococcus aureus–a review of literature. Afr J Med Med Sci. 2011;40(2):97–107.22195376
  • Bolla JR, Sauer JB, Wu D, et al. Direct observation of the influence of cardiolipin and antibiotics on lipid II binding to MurJ. Nat Chem. 2018;10(3):363–371. doi:10.1038/nchem.291929461535
  • Ruiz N. Lipid Flippases for Bacterial Peptidoglycan Biosynthesis. Lipid Insights. 2015;8(Suppl 1):21–31. doi:10.4137/LPI.S3178326792999
  • Mohammadi T, van Dam V, Sijbrandi R, et al. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J. 2011;30(8):1425–1432. doi:10.1038/emboj.2011.6121386816
  • Zapun A, Noirclerc-Savoye M, Helassa N, Vernet T. Peptidoglycan assembly machines: the biochemical evidence. Microb Drug Resist. 2012;18(3):256–260. doi:10.1089/mdr.2011.023622432702
  • Ganchev DN, Hasper HE, Breukink E, de Kruijff B. Size and orientation of the lipid II headgroup as revealed by AFM imaging. Biochemistry. 2006;45(19):6195–6202. doi:10.1021/bi051913e16681392
  • Hasper HE, Kramer NE, Smith JL, et al. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science. 2006;313(5793):1636–1637. doi:10.1126/science.112981816973881
  • Bugg TD, Brandish PE. From peptidoglycan to glycoproteins: common features of lipid-linked oligosaccharide biosynthesis. FEMS Microbiol Lett. 1994;119(3):255–262. doi:10.1111/j.1574-6968.1994.tb06898.x8050708
  • de Leeuw E, Li C, Zeng P, et al. Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II. FEBS Lett. 2010;584(8):1543–1548. doi:10.1016/j.febslet.2010.03.00420214904
  • Schmitt P, Wilmes M, Pugniere M, et al. Insight into invertebrate defensin mechanism of action: oyster defensins inhibit peptidoglycan biosynthesis by binding to lipid II. J Biol Chem. 2010;285(38):29208–29216. doi:10.1074/jbc.M110.14338820605792
  • Schneider T, Kruse T, Wimmer R, et al. Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. Science. 2010;328(5982):1168–1172. doi:10.1126/science.118572320508130
  • Knox JR, Pratt RF. Different modes of vancomycin and D-alanyl-D-alanine peptidase binding to cell wall peptide and a possible role for the vancomycin resistance protein. Antimicrob Agents Chemother. 1990;34(7):1342–1347. doi:10.1128/aac.34.7.13422386365
  • Somma S, Gastaldo L, Corti A. Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp. Antimicrob Agents Chemother. 1984;26(6):917–923. doi:10.1128/aac.26.6.9176240963
  • King A, Phillips I, Kaniga K. Comparative in vitro activity of telavancin (TD-6424), a rapidly bactericidal, concentration-dependent anti-infective with multiple mechanisms of action against Gram-positive bacteria. J Antimicrob Chemother. 2004;53(5):797–803. doi:10.1093/jac/dkh15615028667
  • Woodford N. Novel agents for the treatment of resistant Gram-positive infections. Expert Opin Investig Drugs. 2003;12(2):117–137. doi:10.1517/13543784.12.2.117
  • Schwalbe RS, McIntosh AC, Qaiyumi S, et al. In vitro activity of LY333328, an investigational glycopeptide antibiotic, against enterococci and staphylococci. Antimicrob Agents Chemother. 1996;40(10):2416–2419.8891155
  • Munch D, Engels I, Muller A, et al. Structural variations of the cell wall precursor lipid II and their influence on binding and activity of the lipoglycopeptide antibiotic oritavancin. Antimicrob Agents Chemother. 2015;59(2):772–781. doi:10.1128/AAC.02663-1425403671
  • Singh MP, Petersen PJ, Weiss WJ, et al. Mannopeptimycins, new cyclic glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98: antibacterial and mechanistic activities. Antimicrob Agents Chemother. 2003;47(1):62–69. doi:10.1128/aac.47.1.62-69.200312499170
  • Lee W, Schaefer K, Qiao Y, et al. The Mechanism of Action of Lysobactin. J Am Chem Soc. 2016;138(1):100–103. doi:10.1021/jacs.5b1180726683668
  • O’Connor RD, Singh M, Chang J, et al. Dual Mode of Action for Plusbacin A3 in Staphylococcus aureus. J Phys Chem B. 2017;121(7):1499–1505. doi:10.1021/acs.jpcb.6b1103928135800
  • Reynolds PE, Somner EA. Comparison of the target sites and mechanisms of action of glycopeptide and lipoglycodepsipeptide antibiotics. Drugs Exp Clin Res. 1990;16(8):385–389.2151441
  • Stone KJ, Strominger JL. Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate. Proc Natl Acad Sci U S A. 1971;68(12):3223–3227. doi:10.1073/pnas.68.12.32234332017
  • Vertesy L, Ehlers E, Kogler H, et al. Friulimicins: novel lipopeptide antibiotics with peptidoglycan synthesis inhibiting activity from Actinoplanes friuliensis sp. nov. II. Isolation and structural characterization. J Antibiot (Tokyo). 2000;53(8):816–827. doi:10.7164/antibiotics.53.81611079804
  • Zong Y, Sun X, Gao H, et al. Developing Equipotent Teixobactin Analogues against Drug-Resistant Bacteria and Discovering a Hydrophobic Interaction between Lipid II and Teixobactin. J Med Chem. 2018;61(8):3409–3421. doi:10.1021/acs.jmedchem.7b0124129629769
  • Breukink E, Wiedemann I, van Kraaij C, et al. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science. 1999;286(5448):2361–2364. doi:10.1126/science.286.5448.236110600751
  • Nakano MM, Zuber P. Molecular biology of antibiotic production in Bacillus. Crit Rev Biotechnol. 1990;10(3):223–240. doi:10.3109/073885590090382091702690
  • Schnell N, Entian KD, Schneider U, et al. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature. 1988;333(6170):276–278. doi:10.1038/333276a02835685
  • Smith L, Hasper H, Breukink E, et al. Elucidation of the antimicrobial mechanism of mutacin 1140. Biochemistry. 2008;47(10):3308–3314. doi:10.1021/bi701262z18266322
  • Sashihara T, Kimura H, Higuchi T, et al. A novel lantibiotic, nukacin ISK-1, of Staphylococcus warneri ISK-1: cloning of the structural gene and identification of the structure. Biosci Biotechnol Biochem. 2000;64(11):2420–2428. doi:10.1271/bbb.64.242011193411
  • Demel RA, Peelen T, Siezen RJ, De Kruijff B, Kuipers OP, Nisin Z. mutant nisin Z and lacticin 481 interactions with anionic lipids correlate with antimicrobial activity A monolayer study. Eur J Biochem. 1996;235(1–2):267–274. doi:10.1111/j.1432-1033.1996.00267.x8631341
  • Brötz H, Bierbaum G, Markus A, Molitor E, Sahl HG. Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism? Antimicrob Agents Chemother. 1995;39(3):714–719. doi:10.1128/aac.39.3.7147793878
  • Bauer R, Dicks LM. Mode of action of lipid II-targeting lantibiotics. Int J Food Microbiol. 2005;101(2):201–216. doi:10.1016/j.ijfoodmicro.2004.11.00715862882
  • Montville TJ, Chen Y. Mechanistic action of pediocin and nisin: recent progress and unresolved questions. Appl Microbiol Biotechnol. 1998;50(5):511–519.9917136
  • Somma S, Merati W, Parenti F. Gardimycin, a new antibiotic inhibiting peptidoglycan synthesis. Antimicrob Agents Chemother. 1977;11(3):396–401. doi:10.1128/aac.11.3.396404960
  • Wiedemann I, Bottiger T, Bonelli RR, et al. The mode of action of the lantibiotic lacticin 3147–a complex mechanism involving specific interaction of two peptides and the cell wall precursor lipid II. Mol Microbiol. 2006;61(2):285–296. doi:10.1111/j.1365-2958.2006.05223.x16771847
  • El Ghachi M, Bouhss A, Barreteau H, et al. Colicin M exerts its bacteriolytic effect via enzymatic degradation of undecaprenyl phosphate-linked peptidoglycan precursors. J Biol Chem. 2006;281(32):22761–22772. doi:10.1074/jbc.M60283420016777846
  • Martinez B, Suarez JE, Rodriguez A. Lactococcin 972: a homodimeric lactococcal bacteriocin whose primary target is not the plasma membrane. Microbiology. 1996;142(Pt 9):2393–2398. doi:10.1099/00221287-142-9-239321818877
  • Varney KM, Bonvin AM, Pazgier M, et al. Turning defense into offense: defensin mimetics as novel antibiotics targeting lipid II. PLoS Pathog. 2013;9(11):e1003732. doi:10.1371/journal.ppat.100373224244161
  • Chauhan J, Cardinale S, Fang L, et al. Towards Development of Small Molecule Lipid II Inhibitors as Novel Antibiotics. PLoS One. 2016;11(10):e0164515. doi:10.1371/journal.pone.016451527776124
  • Zhanel GG, Calic D, Schweizer F, et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs. 2010;70(7):859–886. doi:10.2165/11534440-000000000-0000020426497
  • Cornaglia G, Rossolini GM. Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens. Clin Microbiol Infect. 2009;15(3):218–223. doi:10.1111/j.1469-0691.2009.02740.x
  • Stein GE, Wells EM. The importance of tissue penetration in achieving successful antimicrobial treatment of nosocomial pneumonia and complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid. Curr Med Res Opin. 2010;26(3):571–588. doi:10.1185/0300799090351205720055750
  • Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2009;29(11):1275–1279.19873687
  • Zhanel GG, Trapp S, Gin AS, et al. Dalbavancin and telavancin: novel lipoglycopeptides for the treatment of Gram-positive infections. Expert Rev Anti Infect Ther. 2008;6(1):67–81. doi:10.1586/14787210.6.1.6718251665
  • Cavalcanti AB, Goncalves AR, Almeida CS, Bugano DD, Silva E. Teicoplanin versus vancomycin for proven or suspected infection. Cochrane Database Syst Rev. 20106:CD007022.
  • Schneider T, Sahl HG. An oldie but a goodie - cell wall biosynthesis as antibiotic target pathway. Int J Med Microbiol. 2010;300(2–3):161–169. doi:10.1016/j.ijmm.2009.10.00520005776
  • Charneski L, Patel PN, Sym D. Telavancin: a novel lipoglycopeptide antibiotic. Ann Pharmacother. 2009;43(5):928–938. doi:10.1345/aph.1G41719401479
  • Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis. 2006;42(Suppl 1):S25–S34. doi:10.1086/49171116323116
  • Gould IM. Is vancomycin redundant for serious staphylococcal infection? Int J Antimicrob Agents. 2010;36(Suppl 2):S55–S57. doi:10.1016/j.ijantimicag.2010.11.00521129922
  • Hughes D. Exploiting genomics, genetics and chemistry to combat antibiotic resistance. Nat Rev Genet. 2003;4(6):432–441. doi:10.1038/nrg108412776213
  • Jovetic S, Zhu Y, Marcone GL, Marinelli F, Tramper J. beta-Lactam and glycopeptide antibiotics: first and last line of defense? Trends Biotechnol. 2010;28(12):596–604. doi:10.1016/j.tibtech.2010.09.00420970210
  • McGuinness WA, Malachowa N, DeLeo FR. Vancomycin Resistance in Staphylococcus aureus. Yale J Biol Med. 2017;90(2):269–281.28656013
  • Arias CA, Murray BE. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol. 2012;10(4):266–278. doi:10.1038/nrmicro276122421879
  • Whitener CJ, Park SY, Browne FA, et al. Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clin Infect Dis. 2004;38(8):1049–1055. doi:10.1086/38235715095205
  • Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med. 2003;348(14):1342–1347. doi:10.1056/NEJMoa02502512672861
  • Kim A, Kuti JL, Nicolau DP. Review of dalbavancin, a novel semisynthetic lipoglycopeptide. Expert Opin Investig Drugs. 2007;16(5):717–733. doi:10.1517/13543784.16.5.717
  • Patti GJ, Kim SJ, Yu TY, et al. Vancomycin and oritavancin have different modes of action in Enterococcus faecium. J Mol Biol. 2009;392(5):1178–1191. doi:10.1016/j.jmb.2009.06.06419576226
  • Arthur M, Depardieu F, Reynolds P, Courvalin P. Moderate-level resistance to glycopeptide LY333328 mediated by genes of the vanA and vanB clusters in enterococci. Antimicrob Agents Chemother. 1999;43(8):1875–1880.10428906
  • Van Bambeke F. Lipoglycopeptide antibacterial agents in gram-positive infections: a comparative review. Drugs. 2015;75(18):2073–2095. doi:10.1007/s40265-015-0505-826603874
  • Klinker KP, Borgert SJ. Beyond Vancomycin: The Tail of the Lipoglycopeptides. Clin Ther. 2015;37(12):2619–2636. doi:10.1016/j.clinthera.2015.11.00726658277
  • Guskey MT, Tsuji BT. A comparative review of the lipoglycopeptides: oritavancin, dalbavancin, and telavancin. Pharmacotherapy. 2010;30(1):80–94. doi:10.1592/phco.30.1.8020030476
  • Stryjewski ME, O’Riordan WD, Lau WK, et al. Telavancin versus standard therapy for treatment of complicated skin and soft-tissue infections due to gram-positive bacteria. Clin Infect Dis. 2005;40(11):1601–1607. doi:10.1086/42991415889357
  • Stryjewski ME, Chu VH, O’Riordan WD, et al. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study. Antimicrob Agents Chemother. 2006;50(3):862–867. doi:10.1128/AAC.50.3.862-867.200616495243
  • Leonard SN, Szeto YG, Zolotarev M, Grigoryan IV. Comparative in vitro activity of telavancin, vancomycin and linezolid against heterogeneously vancomycin-intermediate Staphylococcus aureus (hVISA). Int J Antimicrob Agents. 2011;37(6):558–561. doi:10.1016/j.ijantimicag.2011.02.00721497067
  • Leuthner KD, Cheung CM, Rybak MJ. Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2006;58(2):338–343. doi:10.1093/jac/dkl23516787952
  • Laohavaleeson S, Kuti JL, Nicolau DP. Telavancin: a novel lipoglycopeptide for serious gram-positive infections. Expert Opin Investig Drugs. 2007;16(3):347–357. doi:10.1517/13543784.16.3.347
  • Stryjewski ME, Graham DR, Wilson SE, et al. Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms. Clin Infect Dis. 2008;46(11):1683–1693. doi:10.1086/58789618444791
  • Rubinstein E, Lalani T, Corey GR, et al. Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens. Clin Infect Dis. 2011;52(1):31–40. doi:10.1093/cid/ciq03121148517
  • Stryjewski ME, Lentnek A, O’Riordan W, et al. A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study. BMC Infect Dis. 2014;14:289. doi:10.1186/1471-2334-14-28924884578
  • Polyzos KA, Mavros MN, Vardakas KZ, et al. Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis. PLoS One. 2012;7(8):e41870. doi:10.1371/journal.pone.004187022916113
  • Torres A, Rubinstein E, Corey GR, Stryjewski ME, Barriere SL. Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure. J Antimicrob Chemother. 2014;69(4):1119–1126. doi:10.1093/jac/dkt49024398339
  • Bosso JA, Nappi J, Rudisill C, et al. Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother. 2011;55(12):5475–5479. doi:10.1128/AAC.00168-1121947388
  • Dunbar LM, Milata J, McClure T, Wasilewski MM, Team SS. Comparison of the efficacy and safety of oritavancin front-loaded dosing regimens to daily dosing: an analysis of the SIMPLIFI trial. Antimicrob Agents Chemother. 2011;55(7):3476–3484. doi:10.1128/AAC.00029-1121537018
  • Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014;370(23):2180–2190. doi:10.1056/NEJMoa131042224897083
  • Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7–10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clin Infect Dis. 2015;60(2):254–262. doi:10.1093/cid/ciu77825294250
  • Corey GR, Arhin FF, Wikler MA, et al. Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2016;48(5):528–534. doi:10.1016/j.ijantimicag.2016.07.01927665522
  • Seltzer E, Dorr MB, Goldstein BP, et al. Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections. Clin Infect Dis. 2003;37(10):1298–1303. doi:10.1086/37901514583862
  • Boucher HW, Wilcox M, Talbot GH, et al. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370(23):2169–2179. doi:10.1056/NEJMoa131048024897082
  • Dunne MW, Puttagunta S, Giordano P, et al. A Randomized Clinical Trial of Single-Dose Versus Weekly Dalbavancin for Treatment of Acute Bacterial Skin and Skin Structure Infection. Clin Infect Dis. 2016;62(5):545–551. doi:10.1093/cid/civ98226611777
  • Raad I, Darouiche R, Vazquez J, et al. Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis. 2005;40(3):374–380. doi:10.1086/42728315668859
  • Dunne MW, Puttagunta S, Sprenger CR, et al. Extended-duration dosing and distribution of dalbavancin into bone and articular tissue. Antimicrob Agents Chemother. 2015;59(4):1849–1855. doi:10.1128/AAC.04550-1425561338
  • de la Cruz M, Gonzalez I, Parish CA, et al. Production of Ramoplanin and Ramoplanin Analogs by Actinomycetes. Front Microbiol. 2017;8:343. doi:10.3389/fmicb.2017.0034328321210
  • Hamburger JB, Hoertz AJ, Lee A, et al. A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface. Proc Natl Acad Sci U S A. 2009;106(33):13759–13764. doi:10.1073/pnas.090468610619666597
  • Cheng M, Huang JX, Ramu S, Butler MS, Cooper MA. Ramoplanin at bactericidal concentrations induces bacterial membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother. 2014;58(11):6819–6827. doi:10.1128/AAC.00061-1425182650
  • Montecalvo MA. Ramoplanin: a novel antimicrobial agent with the potential to prevent vancomycin-resistant enterococcal infection in high-risk patients. J Antimicrob Chemother. 2003;51(Suppl 3):iii31–iii35. doi:10.1093/jac/dkg27412801940
  • Wong MT, Kauffman CA, Standiford HC, et al. Effective suppression of vancomycin-resistant Enterococcus species in asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide, ramoplanin. Clin Infect Dis. 2001;33(9):1476–1482. doi:10.1086/32268711588692
  • Bonner DP, O’Sullivan J, Tanaka SK, Clark JM, Whitney RR. Lysobactin, a novel antibacterial agent produced by Lysobacter sp. II. Biological properties. J Antibiot (Tokyo). 1988;41(12):1745–1751. doi:10.7164/antibiotics.41.17453209466
  • Economou NJ, Cocklin S, Loll PJ. High-resolution crystal structure reveals molecular details of target recognition by bacitracin. Proc Natl Acad Sci U S A. 2013;110(35):14207–14212. doi:10.1073/pnas.130826811023940351
  • Kim SJ, Singh M, Wohlrab A, et al. The isotridecanyl side chain of plusbacin-A3 is essential for the transglycosylase inhibition of peptidoglycan biosynthesis. Biochemistry. 2013;52(11):1973–1979. doi:10.1021/bi400022223421534
  • Schneider T, Gries K, Josten M, et al. The lipopeptide antibiotic Friulimicin B inhibits cell wall biosynthesis through complex formation with bactoprenol phosphate. Antimicrob Agents Chemother. 2009;53(4):1610–1618. doi:10.1128/AAC.01040-0819164139
  • Ling LL, Schneider T, Peoples AJ, et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015;517(7535):455–459. doi:10.1038/nature1409825561178
  • Smith L, Hillman J. Therapeutic potential of type A (I) lantibiotics, a group of cationic peptide antibiotics. Curr Opin Microbiol. 2008;11(5):401–408. doi:10.1016/j.mib.2008.09.00818848642
  • Rogers LA, Whittier EO. Limiting Factors in the Lactic Fermentation. J Bacteriol. 1928;16(4):211–229.16559334
  • Delves-Broughton J, Blackburn P, Evans RJ, Hugenholtz J. Applications of the bacteriocin, nisin. Antonie Van Leeuwenhoek. 1996;69(2):193–202.8775979
  • Cotter PD, Hill C, Ross RP. Bacteriocins: developing innate immunity for food. Nat Rev Microbiol. 2005;3(10):777–788. doi:10.1038/nrmicro127316205711
  • Karakas Sen A, Narbad A, Horn N, et al. Post-translational modification of nisin. The involvement of NisB in the dehydration process. Eur J Biochem. 1999;261(2):524–532. doi:10.1046/j.1432-1327.1999.00303.x10215865
  • Wiedemann I, Breukink E, van Kraaij C, et al. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J Biol Chem. 2001;276(3):1772–1779. doi:10.1074/jbc.M00677020011038353
  • Medeiros-Silva J, Jekhmane S, Paioni AL, et al. High-resolution NMR studies of antibiotics in cellular membranes. Nat Commun. 2018;9(1):3963. doi:10.1038/s41467-018-06314-x30262913
  • Medeiros-Silva J, Jekhmane S, Breukink E, Weingarth M. Towards the native binding modes of Lipid II targeting antibiotics. Chembiochem. 2019. doi:10.1002/cbic.201800796
  • Scherer KM, Spille JH, Sahl HG, Grein F, Kubitscheck U. The lantibiotic nisin induces lipid II aggregation, causing membrane instability and vesicle budding. Biophys J. 2015;108(5):1114–1124. doi:10.1016/j.bpj.2015.01.02025762323
  • Oppedijk SF, Martin NI, Breukink E. Hit ‘em where it hurts: the growing and structurally diverse family of peptides that target lipid-II. Biochim Biophys Acta. 2016;1858(5):947–957. doi:10.1016/j.bbamem.2015.10.02426523408
  • Kramer NE, Smid EJ, Kok J, et al. Resistance of Gram-positive bacteria to nisin is not determined by lipid II levels. FEMS Microbiol Lett. 2004;239(1):157–161. doi:10.1016/j.femsle.2004.08.03315451114
  • Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005;3(3):238–250. doi:10.1038/nrmicro109815703760
  • Lehrer RI, Barton A, Daher KA, et al. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest. 1989;84(2):553–561. doi:10.1172/JCI1141982668334
  • Hadjicharalambous C, Sheynis T, Jelinek R, et al. Mechanisms of alpha-defensin bactericidal action: comparative membrane disruption by Cryptdin-4 and its disulfide-null analogue. Biochemistry. 2008;47(47):12626–12634. doi:10.1021/bi800335e18973303
  • de Leeuw E, Burks SR, Li X, Kao JP, Lu W. Structure-dependent functional properties of human defensin 5. FEBS Lett. 2007;581(3):515–520. doi:10.1016/j.febslet.2006.12.03617250830
  • Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005;49(1):269–275. doi:10.1128/AAC.49.1.269-275.200515616305
  • Zou G, de Leeuw E, Li C, et al. Toward understanding the cationicity of defensins: ARG and LYS versus their noncoded analogs. J Biol Chem. 2007. doi:10.1074/jbc.M611003200.
  • Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3(9):710–720. doi:10.1038/nri118012949495
  • Sass V, Schneider T, Wilmes M, et al. Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci. Infect Immun. 2010;78(6):2793–2800. doi:10.1128/IAI.00688-0920385753
  • Maisetta G, Batoni G, Esin S, et al. Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother. 2003;47(10):3349–3351. doi:10.1128/aac.47.10.3349-3351.200314506056
  • Pazger M, Wei G, Ericksen B, et al. Sometimes It Takes Two to Tango: Contributions of dimerization to functions of human alpha-defensin HNP1 Peptide. J Biol Chem. 2012;287(12):8944–8953. doi:10.1074/jbc.M111.33220522270360
  • Pazgiera M, Hoover DM, Yang D, Lu W, Lubkowski J. Human beta-defensins. Cell Mol Life Sci. 2006;63(11):1294–1313. doi:10.1007/s00018-005-5540-216710608
  • Wei G, de Leeuw E, Pazgier M, et al. Through the looking glass, mechanistic insights from enantiomeric human defensins. J Biol Chem. 2009;284(42):29180–29192. doi:10.1074/jbc.M109.01808519640840
  • Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 2004;22:181–215. doi:10.1146/annurev.immunol.22.012703.10460315032578
  • Andes D, Craig W, Nielsen LA, Kristensen HH. In vivo pharmacodynamic characterization of a novel plectasin antibiotic, NZ2114, in a murine infection model. Antimicrob Agents Chemother. 2009;53(7):3003–3009. doi:10.1128/AAC.01584-0819414576
  • Jiao J, Mao R, Teng D, et al. In vitro and in vivo antibacterial effect of NZ2114 against Streptococcus suis type 2 infection in mice peritonitis models. AMB Express. 2017;7(1):44. doi:10.1186/s13568-017-0347-828220445
  • Klein K, Gronnemose RB, Alm M, et al. Controlled Release of Plectasin NZ2114 from a Hybrid Silicone-Hydrogel Material for Inhibition of Staphylococcus aureus Biofilm. Antimicrob Agents Chemother. 2017;61(7). doi:10.1128/AAC.00604-17.
  • de Leeuw EP. Efficacy of the small molecule inhibitor of Lipid II BAS00127538 against acinetobacter baumannii. Drug Des Devel Ther. 2014;8:1061–1064. doi:10.2147/DDDT.S68020
  • Fletcher S, Yu W, Huang J, et al. Structure-activity exploration of a small-molecule Lipid II inhibitor. Drug Des Devel Ther. 2015;9:2383–2394. doi:10.2147/DDDT.S79504
  • Srinivasan A, Dick JD, Perl TM. Vancomycin resistance in staphylococci. Clin Microbiol Rev. 2002;15(3):430–438. doi:10.1128/cmr.15.3.430-438.200212097250
  • O’Driscoll T, Crank CW. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management. Infect Drug Resist. 2015;8:217–230. doi:10.2147/IDR.S5412526244026
  • Bender JK, Fleige C, Klare I, et al. Detection of a cfr(B) variant in German Enterococcus faecium clinical isolates and the impact on linezolid resistance in enterococcus spp. PLoS One. 2016;11(11):e0167042. doi:10.1371/journal.pone.016704227893790
  • Fiedler S, Bender JK, Klare I, et al. Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M). J Antimicrob Chemother. 2016;71(4):871–881. doi:10.1093/jac/dkv42026682961
  • Derouaux A, Turk S, Olrichs NK, et al. Small molecule inhibitors of peptidoglycan synthesis targeting the lipid II precursor. Biochem Pharmacol. 2011;81(9):1098–1105. doi:10.1016/j.bcp.2011.02.00821356201