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Gramicidin Peptide to Combat Antibiotic Resistance: A Review

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Abstract

Emerging issues of Antibiotic drug resistance have increased the mortality cases all around the world. To deal with the situation natural antimicrobial peptide (AMP) replaces the classic antibiotics. Antimicrobial peptides are short, natural peptides that are active against most bacteria’s, viruses, and fungi etc., The AMP acts as a potent therapeutic agent and finds a new way in the field of drug discovery and pharmaceuticals. One such antimicrobial peptide is gramicidin (gramicidin D and gramicidin S) has high potential of almost 100% killing mechanisms against most of the gram-positive and few gram-negative bacteria’s and fungi which can be used as an alternative antibiotic in the near future. There are reviews focusing only on individual types of gramicidin or particular about their function. Hence, this review focus on providing an overview of antimicrobial peptide gramicidin and its types, structures, its interaction with the membranes/lipid bilayers, functions, stability, and uses. This review also focuses on the challenges to enhance the gramicidin peptide for further use as an efficient effective therapeutic peptide in the pharmaceutical industries.

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Abbreviations

AMP:

Antimicrobial peptide

g-D:

Gramicidin D

g-A:

Gramicidin A

g-B:

Gramicidin B

g-C:

Gramicidin C

g-S:

Gramicidin S

g-AB:

Gramicidin AB

g-BC:

Gramicidin BC

g-AC:

Gramicidin AC

References

  • Abdelhamid HN, Khan MS, Wu HF (2014) Graphene oxide as a nanocarrier for gramicidin (GOGD) for high antibacterial performance. RSC Adv 4:50035–50046

    Article  CAS  Google Scholar 

  • Aguilera-Mendoza L, Marrero-Ponce Y, Tellez-Ibarra R, Llorente-Quesada MT, Salgado J, Barigye SJ, Liu J (2015) Overlap and diversity in antimicrobial peptide databases: compiling a non-redundant set of sequences. Bioinformatics 31:2553–2559

    Article  CAS  PubMed  Google Scholar 

  • Alvarez-Leefmans FJ, Delpire E (2009) Physiology and pathology of chloride transporters and channels in the nervous system: from molecules to diseases. Academic Press, Cambridge

    Google Scholar 

  • Andersen OS, Koeppe RE, Roux B (2005) Gramicidin channels. IEEE Trans Nanobiosci 4:10–20

    Article  Google Scholar 

  • Bahar AA, Ren D (2013) Antimicrobial peptides. Pharmaceuticals 6:1543–1575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bechinger B, Gorr SU (2017) Antimicrobial peptides. J Dent Res 96:254–260

    Article  CAS  PubMed  Google Scholar 

  • Berditsch M, Lux H, Babii O, Afonin S, Ulrich AS (2016) Therapeutic potential of gramicidin S in the treatment of root canal infections. Pharmaceuticals 9:56

    Article  CAS  PubMed Central  Google Scholar 

  • Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bichowsky-Slomnicki L, Berger A, Kurtz J, Katchalski E (1956) The antibacterial action of some basic amino acid copolymers. Arch Biochem Biophys 65:400–413

    Article  PubMed  Google Scholar 

  • Bolintineanu DS, Kaznessis YN (2011) Computational studies of protegrin antimicrobial peptides: a review. Peptides 32:188–201

    Article  CAS  PubMed  Google Scholar 

  • Bourinbaiar AS, Coleman CF (1997) The effect of gramicidin, a topical contraceptive and antimicrobial agent with anti-HIV activity, against herpes simplex viruses type 1 and 2 in vitro. Arch Virol 142:2225–2235

    Article  CAS  PubMed  Google Scholar 

  • Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3:238–250

    Article  CAS  PubMed  Google Scholar 

  • Constantin D (2009) Membrane-mediated repulsion between gramicidin pores. Biochim Biophys Acta BBA 1788:1782–1789

    Article  CAS  PubMed  Google Scholar 

  • Conti E, Stachelhaus T, Marahiel MA, Brick P (1997) Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S. EMBO J 16:4174–4183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • David JM, Rajasekaran AK (2015) Gramicidin A: a new mission for an old antibiotic. J Kidney Cancer VHL 2:15–24

    Article  PubMed  PubMed Central  Google Scholar 

  • David JM, Owens TA, Barwe SP, Rajasekaran AK (2013) Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells. Mol Cancer Ther 12:2296–2307

    Article  CAS  PubMed  Google Scholar 

  • David JM, Owens TA, Inge LJ, Bremner RM, Rajasekaran AK (2014) Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma. Mol Cancer Ther 13:788–799

    Article  CAS  PubMed  Google Scholar 

  • Davies J, Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev MMBR 74:417–433

    Article  CAS  PubMed  Google Scholar 

  • DeLano WL (2002) Pymol: an open-source molecular graphics tool. CCP4 Newsl. Protein Crystallogr 40:82–92

    Google Scholar 

  • Deslouches B, Di YP (2017) Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications. Oncotarget 8:46635–46651

    Article  PubMed  PubMed Central  Google Scholar 

  • Duax WL, Pletnev V, Burkhart BM (2003) Mechanism of ion transport and gating in gramicidin nanotubes. J Mol Struct 647:97–111

    Article  CAS  Google Scholar 

  • Erlanger BF, Goode L (1954) Gramicidin S: relationship of cyclic structure to antibiotic activity. Nature 174:840–841

    Article  CAS  Google Scholar 

  • Gall YM, Konashev MB (2001) The discovery of Gramicidin S: the intellectual transformation of G.F. Gause from biologist to researcher of antibiotics and on its meaning for the fate of Russian genetics. Hist Philos Life Sci 23:137–150

    CAS  PubMed  Google Scholar 

  • Gause GF, Brazhnikova MG (1944) Gramicidin S and its use in the treatment of infected wounds. Nature 154:703

    Article  Google Scholar 

  • Gilmore JL, Yi X, Quan L, Kabanov AV (2008) Novel nanomaterials for clinical neuroscience. J Neuroimmune Pharmacol 3:83–94

    Article  PubMed  PubMed Central  Google Scholar 

  • Gumila C, Ancelin ML, Delort AM, Jeminet G, Vial HJ (1997) Characterization of the potent in vitro and in vivo antimalarial activities of ionophore compounds. Antimicrob Agents Chemother 41:523–529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hancock REW, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557

    Article  CAS  PubMed  Google Scholar 

  • Harold FM, Baarda JR (1967) Gramicidin, valinomycin, and cation permeability of Streptococcus faecalis. J Bacteriol 94:53–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartgerink JD, Granja JR, Milligan RA, Ghadiri MR (1996) Self-assembling peptide nanotubes. J Am Chem Soc 118:43–50

    Article  CAS  Google Scholar 

  • He K, Ludtke SJ, Heller WT, Huang HW (1996) Mechanism of alamethicin insertion into lipid bilayers. Biophys J 71:2669–2679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henderson J (1946) The status of tyrothricin as an antibiotic agent for topical application*†‡*Read in part before the Scientific Section of the Proprietary Association of America, New York N. Y., Dec. 5, 1945.†Johnson & Johnson, New Brunswick, N. J‡The accumulation of much of the data reported herein with respect to the antibacterial and sensitizmg properties of tyrothricin was made possible by a grant from the Johnson & Johnson Research Foundation. J Am Pharm Assoc Sci Ed 35:141–147

  • Herrell WE, Heilman D (1941) Experimental and clinical studies on gramicidin 1. J Clin Invest 20:583–591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang CC, Meng EC, Morris JH, Pettersen EF, Ferrin TE (2014) Enhancing UCSF Chimera through web services. Nucleic Acids Res 42:W478–W484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes D, Karlén A (2014) Discovery and preclinical development of new antibiotics. Ups J Med Sci 119:162–169

    Article  PubMed  PubMed Central  Google Scholar 

  • Jadhav KB, Stein C, Makarewicz O, Pradel G, Lichtenecker RJ, Sack H, Heinemann SH, Arndt HD (2017) Bioactivity of topologically confined gramicidin A dimers. Bioorg Med Chem 25:261–268

    Article  CAS  PubMed  Google Scholar 

  • Jenssen H, Hamill P, Hancock REW (2006) Peptide antimicrobial agents. Clin Microbiol Rev 19:491–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeswani G, Alexander A, Saraf S, Saraf S, Qureshi A (2015) Recent approaches for reducing hemolytic activity of chemotherapeutic agents. J Controlled Release 211:10–21

    Article  CAS  Google Scholar 

  • Kaprel’iants AS, Nikiforov VV, Miroshnikov AI, Snezhkova LG, Eremin VA, Ostrovskiĭ DN (1977) Membranes of bacteria and mechanism of action of the antibiotic gramicidin S. Biokhimiia Mosc Russ 42:329–337

    Google Scholar 

  • Katsu T, Kobayashi H, Fujita Y (1986) Mode of action of gramicidin S on Escherichia coli membrane. Biochim Biophys Acta 860:608–619

    Article  CAS  PubMed  Google Scholar 

  • Kelkar DA, Chattopadhyay A (2007) The gramicidin ion channel: a model membrane protein. Biochim Biophys Acta BBA 1768:2011–2025

    Article  CAS  PubMed  Google Scholar 

  • Killian JA (1992) Gramicidin and gramicidin-lipid interactions. Biochim Biophys Acta 1113:391–425

    Article  CAS  PubMed  Google Scholar 

  • Li W, Tailhades J, O’Brien-Simpson NM, Separovic F, Otvos L, Hossain MA, Wade JD (2014) Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria. Amino Acids 46:2287–2294

    Article  CAS  PubMed  Google Scholar 

  • Llamas-Saiz AL, Grotenbreg GM, Overhand M, van Raaij MJ (2007) Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids. Acta Crystallogr D 63:401–407

    Article  CAS  PubMed  Google Scholar 

  • Mahlapuu M, Håkansson J, Ringstad L, Björn C (2016) Antimicrobial peptides: an emerging category of therapeutic agents. Front Cell Infect Microbiol 6:194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malmsten M (2016) Interactions of antimicrobial peptides with bacterial membranes and membrane components. Curr Top Med Chem 16:16–24

    Article  CAS  PubMed  Google Scholar 

  • Marqus S, Pirogova E, Piva TJ (2017) Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci 24:21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mishra B, Reiling S, Zarena D, Wang G (2017) Host defense antimicrobial peptides as antibiotics: design and application strategies. Curr Opin Chem Biol 38:87–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohamed MF, Abdelkhalek A, Seleem MN (2016) Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus. Sci Rep 6:29707

    Article  PubMed  PubMed Central  Google Scholar 

  • Mösges R, Baues CM, Schröder T, Sahin K (2011) Acute bacterial otitis externa: efficacy and safety of topical treatment with an antibiotic ear drop formulation in comparison to glycerol treatment. Curr Med Res Opin 27:871–878

    Article  CAS  PubMed  Google Scholar 

  • Naumowicz M, Figaszewski Z (2003) Impedance analysis of phosphatidylcholine membranes modified with gramicidin D. Bioelectrochemistry 61:21–27

    Article  CAS  PubMed  Google Scholar 

  • Nelson JW, Zhou Z, Breaker RR (2014) Gramicidin D enhances the antibacterial activity of fluoride. Bioorg Med Chem Lett 24:2969–2971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen LT, Haney EF, Vogel HJ (2011) The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29:464–472

    Article  CAS  PubMed  Google Scholar 

  • North CL, Barranger-Mathys M, Cafiso DS (1995) Membrane orientation of the N-terminal segment of alamethicin determined by solid-state 15N NMR. Biophys J 69:2392–2397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olczak A, Główka ML, Szczesio M, Bojarska J, Wawrzak Z, Duax WL (2010) The first crystal structure of a gramicidin complex with sodium: high-resolution study of a nonstoichiometric gramicidin D-NaI complex. Acta Crystallogr D 66:874–880

    Article  CAS  PubMed  Google Scholar 

  • Otten-Kuipers MA, Roelofsen B, Op den Kamp JA (1995) Stage-dependent effects of analogs of gramicidin A on the growth of Plasmodium falciparum in vitro. Parasitol Res 81:26–31

    Article  CAS  PubMed  Google Scholar 

  • Otten-Kuipers MA, Franssen FF, Nieuwenhuijs H, Overdulve JP, Roelofsen B, Op den Kamp JA (1997) Effect of tryptophan-N-formylated gramicidin on growth of Plasmodium berghei in mice. Antimicrob Agents Chemother 41:1778–1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Otvos L (2000) Antibacterial peptides isolated from insects. J Pept Sci Off Publ Eur Pept Soc 6:497–511

    CAS  Google Scholar 

  • Palm K, Stenberg P, Luthman K, Artursson1 P (1997) Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res 14:568–571

    Article  CAS  PubMed  Google Scholar 

  • Peters BM, Shirtliff ME, Jabra-Rizk MA (2010) Antimicrobial peptides: primeval molecules or future drugs? PLoS Pathog 6:e1001067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pilolli R, Palmisano F, Cioffi N (2012) Gold nanomaterials as a new tool for bioanalytical applications of laser desorption ionization mass spectrometry. Anal Bioanal Chem 402:601–623

    Article  CAS  PubMed  Google Scholar 

  • Pressman BC (1976) Biological applications of ionophores. Annu Rev Biochem 45:501–530

    Article  CAS  PubMed  Google Scholar 

  • Ramírez P, Andreu R, Cuesta A, Calzado CJ, Calvente JJ (2007) Determination of the potential of zero charge of Au(111) modified with thiol monolayers. Anal Chem 79:6473–6479

    Article  CAS  PubMed  Google Scholar 

  • Rawat SS, Kelkar DA, Chattopadhyay A (2004) Monitoring gramicidin conformations in membranes: a fluorescence approach. Biophys J 87:831–843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy KVR, Yedery RD, Aranha C (2004) Antimicrobial peptides: premises and promises. Int J Antimicrob Agents 24:536–547

    Article  CAS  PubMed  Google Scholar 

  • Rozek T, Wegener KL, Bowie JH, Olver IN, Carver JA, Wallace JC, Tyler MJ (2000) The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis the solution structure of aurein 1.2. Eur J Biochem 267:5330–5341

    Article  CAS  PubMed  Google Scholar 

  • Sarkar N, Langley D, Paulus H (1977) Biological function of gramicidin: selective inhibition of RNA polymerase. Proc Natl Acad Sci USA 74:1478–1482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seenath R, Leitch JJ, Su Z, Faragher RJ, Schwan AL, Lipkowski J (2017) Measurements of surface concentration and charge number per adsorbed molecule for a thiolipid monolayer tethered to the Au(111) surface by a long hydrophilic chain. J Electroanal Chem 793:203–208

    Article  CAS  Google Scholar 

  • Sieber SA, Marahiel MA (2005) Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chem Rev 105:715–738

    Article  CAS  PubMed  Google Scholar 

  • Stachelhaus T, Marahiel MA (1995) Modular structure of peptide synthetases revealed by dissection of the multifunctional enzyme GrsA. J Biol Chem 270:6163–6169

    Article  CAS  PubMed  Google Scholar 

  • Su Z, Leitch JJ, Faragher RJ, Schwan AL, Lipkowski J (2017) Gramicidin A ion channel formation in model phospholipid bilayers tethered to gold (111) electrode surfaces. Electrochim Acta 243:364–373

    Article  CAS  Google Scholar 

  • Sumi CD, Yang BW, Yeo IC, Hahm YT (2014) Antimicrobial peptides of the genus Bacillus: a new era for antibiotics. Can J Microbiol 61:93–103

    Article  CAS  PubMed  Google Scholar 

  • Swierstra J, Kapoerchan V, Knijnenburg A, van Belkum A, Overhand M (2016) Structure, toxicity and antibiotic activity of gramicidin S and derivatives. Eur J Clin Microbiol Infect Dis 35:763–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Townsley LE, Tucker WA, Sham S, Hinton JF (2001) Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry 40:11676–11686

    Article  CAS  PubMed  Google Scholar 

  • Wallace BA (1986) Structure of gramicidin A. Biophys J 49:295–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan Y, Stanovych A, Gori D, Zirah S, Kouklovsky C, Alezra V (2018) β,γ-diamino acids as building blocks for new analogues of Gramicidin S: synthesis and biological activity. Eur J Med Chem 149:122–128

    Article  CAS  PubMed  Google Scholar 

  • Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5:905–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wipf P, Skoda EM, Mann A (2015) Chap. 11—conformational restriction and steric hindrance in medicinal chemistry. In: Wermuth CG, Aldous D, Raboisson P, Rognan D (eds) The practice of medicinal chemistry, 4th edn. Academic Press, San Diego, pp 279–299

    Chapter  Google Scholar 

  • Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 36:D901–D906

    Article  CAS  PubMed  Google Scholar 

  • Yeaman MR, Yount NY (2003) Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55:27–55

    Article  CAS  PubMed  Google Scholar 

  • Yeung ATY, Gellatly SL, Hancock REW (2011) Multifunctional cationic host defence peptides and their clinical applications. Cell Mol Life Sci CMLS 68:2161–2176

    Article  CAS  PubMed  Google Scholar 

  • Yonezawa H, Okamoto K, Tomokiyo K, Izumiya N (1986) Mode of antibacterial action by gramicidin S. J Biochem (Tokyo) 100:1253–1259

    Article  CAS  Google Scholar 

  • Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Gallo RL (2016) Antimicrobial peptides. Curr Biol 26:R14–R19

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank VIT for providing ‘VIT SEED Grant’ for carrying out this review work.

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Correspondence to R. Rajasekaran.

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Pavithrra, G., Rajasekaran, R. Gramicidin Peptide to Combat Antibiotic Resistance: A Review. Int J Pept Res Ther 26, 191–199 (2020). https://doi.org/10.1007/s10989-019-09828-0

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