Skip to main content

Advertisement

Log in

Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria

  • Minireview Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

The increasing resistance of pathogens to antibiotics causes a huge clinical burden that places great demands on academic researchers and the pharmaceutical industry for resolution. Antimicrobial peptides, part of native host defense, have emerged as novel potential antibiotic alternatives. Among the different classes of antimicrobial peptides, proline-rich antimicrobial peptides, predominantly sourced from insects, have been extensively investigated to study their specific modes of action. In this review, we focus on recent developments in these peptides. They show a variety of modes of actions, including mechanism shift at high concentration, non-lytic mechanisms, as well as possessing different intracellular targets and lipopolysaccharide binding activity. Furthermore, proline-rich antimicrobial peptides display the ability to not only modulate the immune system via cytokine activity or angiogenesis but also possess properties of penetrating cell membranes and crossing the blood brain barrier suggesting a role as potential novel carriers. Ongoing studies of these peptides will likely lead to the development of more potent antimicrobial peptides that may serve as important additions to the armoury of agents against bacterial infection and drug delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AMPs:

Antimicrobial peptides

PrAMPs:

Proline-rich antimicrobial peptides

LPS:

Lipopolysaccharide

CPPs:

Cell penetrating peptides

BBB:

Blood brain barrier

References

  • Agerberth B, Lee JY, Bergman T, Carlquist M, Boman HG, Mutt V, Jornvall H (1991) Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur J Biochem 202:849–854

    PubMed  CAS  Google Scholar 

  • Anbanandam A, Albarado DC, Tirziu DC, Simons M, Veeraraghavan S (2008) Molecular basis for proline- and arginine-rich peptide inhibition of proteasome. J Mol Biol 384:219–227

    PubMed  CAS  PubMed Central  Google Scholar 

  • Avitabile C, D’Andrea LD, Romanelli A (2014) Circular dichroism studies on the interactions of antimicrobial peptides with bacterial cells. Sci Rep 4:4293

    PubMed  PubMed Central  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Baumann T, Kämpfer U, Schürch S, Schaller J, Largiadèr C, Nentwig W, Kuhn-Nentwig L (2010) Ctenidins: antimicrobial glycine-rich peptides from the hemocytes of the spider Cupiennius salei. Cell Mol Life Sci 67:2787–2798

    PubMed  CAS  Google Scholar 

  • Bencivengo A-M, Cudic M, Hoffmann R, Otvos L Jr (2001) The efficacy of the antibacterial peptide, pyrrhocoricin, is finely regulated by its amino acid residues and active domains. Lett Pept Sci 8:201–209

    CAS  Google Scholar 

  • Benincasa M, Pelillo C, Zorzet S, Garrovo C, Biffi S, Gennaro R, Scocchi M (2010) The proline-rich peptide Bac7(1–35) reduces mortality from Salmonella typhimurium in a mouse model of infection. BMC Microbiol 10:178

    PubMed  PubMed Central  Google Scholar 

  • Berthold N, Hoffmann R (2014) Cellular uptake of apidaecin 1b and related analogs in Gram-negative bacteria reveals novel antibacterial mechanism for proline-rich antimicrobial peptides. Protein Pept Lett 21:391–398

    PubMed  CAS  Google Scholar 

  • Boman HG, Agerberth B, Boman A (1993) Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine. Infect Immun 61:2978–2984

    PubMed  CAS  PubMed Central  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Brötz H, Bierbaum G, Leopold K, Reynolds PE, Sahl H-G (1998) The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob Agents Chemother 42:154–160

    PubMed  PubMed Central  Google Scholar 

  • Bulet P, Dimarcq JL, Hetru C, Lagueux M, Charlet M, Hegy G, Van Dorsselaer A, Hoffmann JA (1993) A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution. J Biol Chem 268:14893–14897

    PubMed  CAS  Google Scholar 

  • Bulet P, Hetru C, Dimarcq JL, Hoffmann D (1999) Antimicrobial peptides in insects; structure and function. Dev Comp Immunol 23:329–344

    PubMed  CAS  Google Scholar 

  • Butler MS, Blaskovich MA, Cooper MA (2013) Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo) 66:571–591

    CAS  Google Scholar 

  • Cannon B (2014) Microbiology: resistance fighters. Nature 509:S6–S8

    PubMed  CAS  Google Scholar 

  • Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395

    PubMed  CAS  Google Scholar 

  • Cassone M, Otvos L (2010) Synergy among antibacterial peptides and between peptides and small-molecule antibiotics. Expert Rev Anti Infect Ther 8:703–716

    PubMed  CAS  Google Scholar 

  • Cassone M, Frith N, Vogiatzi P, Wade JD, Otvos L (2009) Induced resistance to the designer proline-rich antimicrobial peptide A3-APO does not involve changes in the intracellular target DnaK. Int J Pept Res Ther 15:121–128

    CAS  Google Scholar 

  • Casteels P, Ampe C, Jacobs F, Vaeck M, Tempst P (1989) Apidaecins: antibacterial peptides from honeybees. EMBO J 8:2387

    PubMed  CAS  PubMed Central  Google Scholar 

  • Chan DI, Prenner EJ, Vogel HJ (2006) Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action. Biochim Biophys Acta 1758:1184–1202

    PubMed  CAS  Google Scholar 

  • Chen W, Luo L (2009) Classification of antimicrobial peptide using diversity measure with quadratic discriminant analysis. J Microbiol Methods 78:94–96

    PubMed  CAS  Google Scholar 

  • Chesnokova LS, Slepenkov SV, Witt SN (2004) The insect antimicrobial peptide, l-pyrrhocoricin, binds to and stimulates the ATPase activity of both wild-type and lidless DnaK. FEBS Lett 565:65–69

    PubMed  CAS  Google Scholar 

  • Chitnis SN, Prasad KN, Bhargava PM (1987) Bacteriolytic activity of seminalplasmin. J Gen Microbiol 133:1265–1271

    PubMed  CAS  Google Scholar 

  • Chitnis SN, Prasad KSN, Bhargava PM (1990) Isolation and characterization of autolysis-defective mutants of Escherichia coli that are resistant to the lytic activity of seminalplasmin. J Gen Microbiol 136:463–469

    PubMed  CAS  Google Scholar 

  • Cho JH, Park CB, Yoon YG, Kim SC (1998) Lumbricin I, a novel proline-rich antimicrobial peptide from the earthworm: purification, cDNA cloning and molecular characterization. Biochim Biophys Acta 1408:67–76

    PubMed  CAS  Google Scholar 

  • Cully M (2014) Public health: the politics of antibiotics. Nature 509:S16–S17

    PubMed  CAS  Google Scholar 

  • Dagan A, Efron L, Gaidukov L, Mor A, Ginsburg H (2002) In vitro antiplasmodium effects of dermaseptin S4 derivatives. Antimicrob Agents Chemother 46:1059–1066

    PubMed  CAS  PubMed Central  Google Scholar 

  • de Souza Cândido E, e Silva Cardoso MH, Sousa DA, Viana JC, de Oliveira-Júnior NG, Miranda V, Franco OL (2014) The use of versatile plant antimicrobial peptides in agribusiness and human health. Peptides 55:65–78

    PubMed  Google Scholar 

  • Delgado MA, Rintoul MR, Farı́as RN, Salomón RA (2001) Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25. J Bacteriol 183:4543–4550

    PubMed  CAS  PubMed Central  Google Scholar 

  • Destoumieux D, Munoz M, Bulet P, Bachere E (2000) Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda). Cell Mol Life Sci 57:1260–1271

    PubMed  CAS  Google Scholar 

  • Dimarcq J-L, Bulet P, Hetru C, Hoffmann J (1998) Cysteine-rich antimicrobial peptides in invertebrates. Pept Sci 47:465–477

    CAS  Google Scholar 

  • Dmitriev RI, Ropiak HM, Yashunsky DV, Ponomarev GV, Zhdanov AV, Papkovsky DB (2010) Bactenecin 7 peptide fragment as a tool for intracellular delivery of a phosphorescent oxygen sensor. FEBS J 277:4651–4661

    PubMed  CAS  Google Scholar 

  • Dong N, Ma Q, Shan A, Lv Y, Hu W, Gu Y, Li Y (2012) Strand length-dependent antimicrobial activity and membrane-active mechanism of arginine- and valine-rich β-hairpin-like antimicrobial peptides. Antimicrob Agents Chemother 56:2994–3003

    PubMed  CAS  PubMed Central  Google Scholar 

  • El-Andaloussi S, Järver P, Johansson HJ, Langel Ü (2007) Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study. Biochem J 407:285–292

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fasano A (1998) Innovative strategies for the oral delivery of drugs and peptides. Trends Biotechnol 16:152–157

    PubMed  CAS  Google Scholar 

  • Fernandez DI, Gehman JD, Separovic F (2009) Membrane interactions of antimicrobial peptides from Australian frogs. Biochim Biophys Acta 1788:1630–1638

    PubMed  CAS  Google Scholar 

  • Fernández-Vidal M, Jayasinghe S, Ladokhin AS, White SH (2007) Folding amphipathic helices into membranes: amphiphilicity trumps hydrophobicity. J Mol Biol 370:459–470

    PubMed  PubMed Central  Google Scholar 

  • Fox JL (2013) Antimicrobial peptides stage a comeback. Nat Biotechnol 31:379–382

    PubMed  CAS  Google Scholar 

  • Gaczynska M, Osmulski PA, Gao Y, Post MJ, Simons M (2003) Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity. Biochemistry (Mosc) 42:8663–8670

    CAS  Google Scholar 

  • Gallo RL, Ono M, Povsic T, Page C, Eriksson E, Klagsbrun M, Bernfield M (1994) Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc Natl Acad Sci USA 91:11035–11039

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gammon K (2014) Drug discovery: leaving no stone unturned. Nature 509:S10–S12

    PubMed  CAS  Google Scholar 

  • Gazit E, Boman A, Boman HG, Shai Y (1995) Interaction of the mammalian antibacterial peptide cecropin P1 with phospholipid vesicles. Biochemistry (Mosc) 34:11479–11488

    CAS  Google Scholar 

  • Gennaro R, Skerlavaj B, Romeo D (1989) Purification, composition, and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect Immun 57:3142–3146

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gennaro R, Zanetti M, Benincasa M, Podda E, Miani M (2002) Pro-rich antimicrobial peptides from animals: structure, biological functions and mechanism of action. Curr Pharm Des 8:763–778

    PubMed  CAS  Google Scholar 

  • Ghosh JK, Shaool D, Guillaud P, Cicéron L, Mazier D, Kustanovich I, Shai Y, Mor A (1997) Selective cytotoxicity of dermaseptin S3 toward intraerythrocytic Plasmodium falciparum and the underlying molecular basis. J Biol Chem 272:31609–31616

    PubMed  CAS  Google Scholar 

  • Giuliani A, Pirri G, Nicoletto S (2007) Antimicrobial peptides: an overview of a promising class of therapeutics. Cent Eur J Biol 2:1–33

    CAS  Google Scholar 

  • Hallock KJ, Lee D-K, Ramamoorthy A (2003) MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain. Biophys J 84:3052–3060

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hancock REW (1997) Peptide antibiotics. Lancet 349:418–422

    PubMed  CAS  Google Scholar 

  • Hancock REW, Nijnik A, Philpott DJ (2012) Modulating immunity as a therapy for bacterial infections. Nat Rev Microbiol 10:243–254

    PubMed  CAS  Google Scholar 

  • He K, Ludtke SJ, Worcester DL, Huang HW (1996) Neutron scattering in the plane of membranes: structure of alamethicin pores. Biophys J 70:2659–2666

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hede K (2014) Antibiotic resistance: an infectious arms race. Nature 509:S2–S3

    PubMed  Google Scholar 

  • Henzler Wildman KA, Lee D-K, Ramamoorthy A (2003) Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry (Mosc) 42:6545–6558

    CAS  Google Scholar 

  • Hernandez-Gordillo V, Geisler I, Chmielewski J (2014) Dimeric unnatural polyproline-rich peptides with enhanced antibacterial activity. Bioorg Med Chem Lett 24:556–559

    PubMed  CAS  Google Scholar 

  • Hilchie AL, Wuerth K, Hancock REW (2013) Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. Nat Chem Biol 9:761–768

    PubMed  CAS  Google Scholar 

  • Hsueh P-R (2012) Study for monitoring antimicrobial resistance trends (SMART) in the Asia-Pacific region, 2002–2010. Int J Antimicrob Agents 40:S1–S3

    PubMed  CAS  Google Scholar 

  • Ilić N, Novković M, Guida F, Xhindoli D, Benincasa M, Tossi A, Juretić D (2013) Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences. Biochim Biophys Acta 1828:1004–1012

    PubMed  Google Scholar 

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

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kanthor R (2014) Diagnostics: detection drives defence. Nature 509:S14–S15

    PubMed  CAS  Google Scholar 

  • Kavanagh K, Dowd S (2004) Histatins: antimicrobial peptides with therapeutic potential. J Pharm Pharmacol 56:285–289

    PubMed  CAS  Google Scholar 

  • Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L Jr (2001) The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry (Mosc) 40:3016–3026

    CAS  Google Scholar 

  • Kraus D, Peschel A (2006) Molecular mechanisms of bacterial resistance to antimicrobial peptides. Curr Top Microbiol Immunol 306:231–250

    PubMed  CAS  Google Scholar 

  • Lalatsa A, Schatzlein AG, Uchegbu IF (2014) Strategies to deliver peptide drugs to the brain. Mol Pharm 11:1081–1093

    PubMed  CAS  Google Scholar 

  • Lehrer R, Barton A, Daher K, Harwig S, Ganz T, Selsted M (1989) Interaction of human defensins with Escherichia coli mechanism of bactericidal activity. J Clin Invest 84:553

    PubMed  CAS  PubMed Central  Google Scholar 

  • Li CY, Song YL (2010) Proline-rich domain of penaeidin molecule exhibits autocrine feature by attracting penaeidin-positive granulocytes toward the wound-induced inflammatory site. Fish Shellfish Immunol 29:1044–1052

    PubMed  CAS  Google Scholar 

  • Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry (Mosc) 35:13723–13728

    CAS  Google Scholar 

  • Marr AK, Gooderham WJ, Hancock REW (2006) Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol 6:468–472

    PubMed  CAS  Google Scholar 

  • Matsuzaki K (1999) Why and how are peptide–lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochim Biophys Acta 1462:1–10

    PubMed  CAS  Google Scholar 

  • Matsuzaki K, Murase O, Fujii N, Miyajima K (1996) An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry (Mosc) 35:11361–11368

    CAS  Google Scholar 

  • Matsuzaki K, Sugishita K, Ishibe N, Ueha M, Nakata S, Miyajima K, Epand RM (1998) Relationship of membrane curvature to the formation of pores by magainin 2. Biochemistry (Mosc) 37:11856–11863

    CAS  Google Scholar 

  • Naito A, Nagao T, Norisada K, Mizuno T, Tuzi S, Saitô H (2000) Conformation and dynamics of melittin bound to magnetically oriented lipid bilayers by solid-state 31P and 13C NMR spectroscopy. Biophys J 78:2405–2417

    PubMed  CAS  PubMed Central  Google Scholar 

  • Narayanan S, Modak JK, Ryan CS, Garcia-Bustos J, Davies JK, Roujeinikova A (2014) Mechanism of Escherichia coli resistance to pyrrhocoricin. Antimicrob Agents Chemother 58:2754–2762

    PubMed  CAS  Google Scholar 

  • Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y (1999) Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341:501–513

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ostorhazi E, Holub MC, Rozgonyi F, Harmos F, Cassone M, Wade JD, Otvos L Jr (2011) Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved. Int J Antimicrob Agents 37:480–484

    PubMed  CAS  Google Scholar 

  • Ostorhazi E, Voros E, Nemes-Nikodem E, Wade JD, Otvos L (2013) Rapid systemic and local treatments with the antibacterial peptide dimer A3-APO and its monomeric metabolite eliminate bacteria and reduce inflammation in intradermal lesions infected with Propionibacterium acnes and meticillin-resistant Staphyloccus aureus. Int J Antimicrob Agents 42:537–543

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

    PubMed  CAS  Google Scholar 

  • Otvos L, Otvos I, Rogers ME, Consolvo PJ, Condie BA, Lovas S, Bulet P, Blaszczyk-Thurin M (2000) Interaction between heat shock proteins and antimicrobial peptides. Biochemistry (Mosc) 39:14150–14159

    CAS  Google Scholar 

  • Otvos L (2002) The short proline-rich antibacterial peptide family. Cell Mol Life Sci 59:1138–1150

    PubMed  CAS  Google Scholar 

  • Otvos L (2005) Antibacterial peptides and proteins with multiple cellular targets. J Pept Sci 11:697–706

    PubMed  CAS  Google Scholar 

  • Otvos L, Cudic M, Chua BY, Deliyannis G, Jackson DC (2004) An insect antibacterial peptide-based drug delivery system. Mol Pharm 1:220–232

    PubMed  CAS  Google Scholar 

  • Otvos L, Flick-Smith H, Fox M, Ostorhazi E, Dawson RM, Wade JD (2014) The designer proline-rich antibacterial peptide A3-APO prevents Bacillus anthracis mortality by deactivating bacterial toxins. Protein Pept Lett 21:374–381

    PubMed  CAS  Google Scholar 

  • Patrzykat A, Friedrich CL, Zhang L, Mendoza V, Hancock REW (2002) Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. Antimicrob Agents Chemother 46:605–614

    PubMed  CAS  PubMed Central  Google Scholar 

  • Paulsen VS, Blencke H-M, Benincasa M, Haug T, Eksteen JJ, Styrvold OB, Scocchi M, Stensvåg K (2013) Structure–activity relationships of the antimicrobial peptide arasin 1—and mode of action studies of the N-terminal, proline-rich region. PLoS ONE 8:e53326

    PubMed  CAS  PubMed Central  Google Scholar 

  • Pelillo C, Benincasa M, Scocchi M, Gennaro R, Tossi A, Pacor S (2014) Cellular internalization and cytotoxicity of the antimicrobial proline-rich peptide Bac7(1–35) in monocytes/macrophages, and its activity against phagocytosed Salmonella typhimurium. Protein Pept Lett 21:382–390

    PubMed  CAS  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  • Podda E, Benincasa M, Pacor S, Micali F, Mattiuzzo M, Gennaro R, Scocchi M (2006) Dual mode of action of Bac7, a proline-rich antibacterial peptide. Biochim Biophys Acta 1760:1732–1740

    PubMed  CAS  Google Scholar 

  • Pouny Y, Rapaport D, Mor A, Nicolas P, Shai Y (1992) Interaction of antimicrobial dermaseptin and its fluorescently labeled analogs with phospholipid membranes. Biochemistry (Mosc) 31:12416–12423

    CAS  Google Scholar 

  • Powers J-PS, Hancock REW (2003) The relationship between peptide structure and antibacterial activity. Peptides 24:1681–1691

    PubMed  CAS  Google Scholar 

  • Pushpanathan M, Gunasekaran P, Rajendhran J (2013) Antimicrobial peptides: versatile biological properties. Int J Pept 2013:15

    Google Scholar 

  • Rappocciolo E (2004) Antimicrobial peptides as carriers of drugs. Drug Discov Today 9:470

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Rolland JL, Abdelouahab M, Dupont J, Lefevre F, Bachere E, Romestand B (2010) Stylicins, a new family of antimicrobial peptides from the Pacific blue shrimp Litopenaeus stylirostris. Mol Immunol 47:1269–1277

    PubMed  CAS  Google Scholar 

  • Rozgonyi F, Szabo D, Kocsis B, Ostorhazi E, Abbadessa G, Cassone M, Wade JD, Otvos L (2009) The antibacterial effect of a proline-rich antibacterial peptide A3-APO. Curr Med Chem 16:3996–4002

    PubMed  CAS  Google Scholar 

  • Runti G, MdC Lopez Ruiz, Stoilova T, Hussain R, Jennions M, Choudhury HG, Benincasa M, Gennaro R, Beis K, Scocchi M (2013) Functional characterization of SbmA, a bacterial inner membrane transporter required for importing the antimicrobial peptide Bac7(1–35). J Bacteriol 195:5343–5351

    PubMed  CAS  PubMed Central  Google Scholar 

  • Sadler K, Eom KD, Yang J-L, Dimitrova Y, Tam JP (2002) Translocating proline-rich peptides from the antimicrobial peptide bactenecin 7. Biochemistry (Mosc) 41:14150–14157

    CAS  Google Scholar 

  • Salomón RA, Farías RN (1992) Microcin 25, a novel antimicrobial peptide produced by Escherichia coli. J Bacteriol 174:7428–7435

    PubMed  PubMed Central  Google Scholar 

  • Scheit KH, Reddy ESP, Bhargava PM (1979) Seminalplasmin is a potent inhibitor of E. coli RNA polymerase in vitro. Nature 279:728–731

    PubMed  CAS  Google Scholar 

  • Scocchi M, Tossi A, Gennaro R (2011) Proline-rich antimicrobial peptides: converging to a non-lytic mechanism of action. Cell Mol Life Sci 68:2317–2330

    PubMed  CAS  Google Scholar 

  • Shai Y (1995) Molecular recognition between membrane-spanning polypeptides. Trends Biochem Sci 20:460–464

    PubMed  CAS  Google Scholar 

  • Shai Y (1999) Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462:55–70

    PubMed  CAS  Google Scholar 

  • Shamova O, Brogden KA, Zhao C, Nguyen T, Kokryakov VN, Lehrer RI (1999) Purification and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes. Infect Immun 67:4106–4111

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shen X, Ye G, Cheng X, Yu C, Altosaar I, Hu C (2010) Characterization of an abaecin-like antimicrobial peptide identified from a Pteromalus puparum cDNA clone. J Invertebr Pathol 105:24–29

    PubMed  CAS  Google Scholar 

  • Shi J, Ross CR, Chengappa MM, Sylte MJ, McVey DS, Blecha F (1996) Antibacterial activity of a synthetic peptide (PR-26) derived from PR-39, a proline-arginine-rich neutrophil antimicrobial peptide. Antimicrob Agents Chemother 40:115–121

    PubMed  CAS  PubMed Central  Google Scholar 

  • Smith R, Separovic F, Bennett FC, Cornell BA (1992) Melittin-induced changes in lipid multilayers. A solid-state NMR study. Biophys J 63:469–474

    PubMed  CAS  PubMed Central  Google Scholar 

  • Splith K, Neundorf I (2011) Antimicrobial peptides with cell-penetrating peptide properties and vice versa. Eur Biophys J 40:387–397

    PubMed  CAS  Google Scholar 

  • Stalmans S, Wynendaele E, Bracke N, Knappe D, Hoffmann R, Peremans K, Polis I, Burvenich C, De Spiegeleer B (2014) Blood–brain barrier transport of short proline-rich antimicrobial peptides. Protein Pept Lett 21:399–406

    PubMed  CAS  Google Scholar 

  • Stensvag K, Haug T, Sperstad SV, Rekdal O, Indrevoll B, Styrvold OB (2008) Arasin 1, a proline-arginine-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. Dev Comp Immunol 32:275–285

    PubMed  CAS  Google Scholar 

  • Stewart KM, Horton KL, Kelley SO (2008) Cell-penetrating peptides as delivery vehicles for biology and medicine. Org Biomol Chem 6:2242–2255

    PubMed  CAS  Google Scholar 

  • Subbalakshmi C, Sitaram N (1998) Mechanism of antimicrobial action of indolicidin. FEMS Microbiol Lett 160:91–96

    PubMed  CAS  Google Scholar 

  • Szabo D, Ostorhazi E, Binas A, Rozgonyi F, Kocsis B, Cassone M, Wade JD, Nolte O, Otvos L Jr (2010) The designer proline-rich antibacterial peptide A3-APO is effective against systemic Escherichia coli infections in different mouse models. Int J Antimicrob Agents 35:357–361

    PubMed  CAS  Google Scholar 

  • Tian W, Li B, Zhang X, Dang W, Wang X, Tang H, Wang L, Cao H, Chen T (2012) Suppression of tumor invasion and migration in breast cancer cells following delivery of siRNA against Stat3 with the antimicrobial peptide PR39. Oncol Rep 28:1362–1368

    PubMed  CAS  Google Scholar 

  • Végh AG, Nagy K, Bálint Z, Kerényi Á, Rákhely G, Váró G, Szegletes Z (2011) Effect of antimicrobial peptide-amide: indolicidin on biological membranes. J Biomed Biotechnol 2011

  • Wilson SS, Wiens ME, Smith JG (2013) Antiviral mechanisms of human defensins. J Mol Biol 425:4965–4980

    PubMed  CAS  Google Scholar 

  • Wong H, Bowie JH, Carver JA (1997) The solution structure and activity of caerin 1.1, an antimicrobial peptide from the Australian green tree frog, Litoria splendida. Eur J Biochem 247:545–557

    PubMed  CAS  Google Scholar 

  • Wu M, Maier E, Benz R, Hancock REW (1999) Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli. Biochemistry (Mosc) 38:7235–7242

    CAS  Google Scholar 

  • Yamaguchi S, Huster D, Waring A, Lehrer RI, Kearney W, Tack BF, Hong M (2001) Orientation and dynamics of an antimicrobial peptide in the lipid bilayer by solid-state NMR spectroscopy. Biophys J 81:2203–2214

    PubMed  CAS  PubMed Central  Google Scholar 

  • Yamaguchi S, Hong T, Waring A, Lehrer RI, Hong M (2002) Solid-state NMR investigations of peptide–lipid interaction and orientation of a β-sheet antimicrobial peptide, protegrin. Biochemistry (Mosc) 41:9852–9862

    CAS  Google Scholar 

  • Yang L, Weiss TM, Lehrer RI, Huang HW (2000) Crystallization of antimicrobial pores in membranes: magainin and protegrin. Biophys J 79:2002–2009

    PubMed  CAS  PubMed Central  Google Scholar 

  • Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J 81:1475–1485

    PubMed  PubMed Central  Google Scholar 

  • Yu P-L, Cross ML, Haverkamp RG (2010) Antimicrobial and immunomodulatory activities of an ovine proline/arginine-rich cathelicidin. Int J Antimicrob Agents 35:288–291

    PubMed  CAS  Google Scholar 

  • Zahn M, Berthold N, Kieslich B, Knappe D, Hoffmann R, Sträter N (2013) Structural studies on the forward and reverse binding modes of peptides to the chaperone DnaK. J Mol Biol 425:2463–2479

    PubMed  CAS  Google Scholar 

  • Zahn M, Kieslich B, Berthold N, Knappe D, Hoffmann R, Strater N (2014) Structural identification of DnaK binding sites within bovine and sheep bactenecin Bac7. Protein Pept Lett 21:407–412

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zhang R, Eggleston K, Rotimi V, Zeckhauser RJ (2006) Antibiotic resistance as a global threat: evidence from China, Kuwait and the United States. Glob Health 2:6

    Google Scholar 

  • Zhang L, Falla TJ (2006) Antimicrobial peptides: therapeutic potential. Expert Opin Pharmacother 7:653–663

    PubMed  CAS  Google Scholar 

  • Zhou Y, Chen WN (2011) iTRAQ-coupled 2-D LC–MS/MS analysis of membrane protein profile in Escherichia coli incubated with apidaecin IB. PLoS ONE 6:e20442

    PubMed  CAS  PubMed Central  Google Scholar 

  • Zhu Y-G, Johnson TA, Su J-Q, Qiao M, Guo G-X, Stedtfeld RD, Hashsham SA, Tiedje JM (2013) Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proc Natl Acad Sci USA 110:3435–3440

    PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

We acknowledge partial support of the studies undertaken in the authors’ laboratory by the Australian Research Council (DP150103522) to MAH and JDW and the National Health and Medical Research Council (NHMRC) Grant APP1029878 to NMOBS. JDW is an NHMRC (Australia) Principal Research Fellow. Research at the FNI was supported by the Victorian Government’s Operational Infrastructure Support Program.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The manuscript does not contain clinical studies or patient data.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John D. Wade.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, W., Tailhades, J., O’Brien-Simpson, N.M. et al. Proline-rich antimicrobial peptides: potential therapeutics against antibiotic-resistant bacteria. Amino Acids 46, 2287–2294 (2014). https://doi.org/10.1007/s00726-014-1820-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-014-1820-1

Keywords

Navigation