Publication Cover
Biofouling
The Journal of Bioadhesion and Biofilm Research
Volume 29, 2013 - Issue 4
5,207
Views
85
CrossRef citations to date
0
Altmetric
Articles

Mini-review: Lactoferrin: a bioinspired, anti-biofilm therapeutic

&
Pages 443-455 | Received 12 Oct 2012, Accepted 25 Jan 2013, Published online: 10 Apr 2013

References

  • Ammons , MC , Ward , LS , Dowd , S and James , GA . 2011 . Combined treatment of Pseudomonas aeruginosa biofilm with lactoferrin and xylitol inhibits the ability of bacteria to respond to damage resulting from lactoferrin iron chelation . Int J Antimicrob Agents , 37 : 316 – 323 .
  • Ammons , MC , Ward , LS , Fisher , ST , Wolcott , RD and James , GA . 2009 . In vitro susceptibility of established biofilms composed of a clinical wound isolate of Pseudomonas aeruginosa treated with lactoferrin and xylitol . Int J Antimicrob Agents , 33 : 230 – 236 .
  • Ammons , MC , Ward , LS and James , GA . 2011 . Anti-biofilm efficacy of a lactoferrin/xylitol wound hydrogel used in combination with silver wound dressings . Int Wound J , 8 : 268 – 273 .
  • Andersen , JH , Osbakk , SA , Vorland , LH , Traavik , T and Gutteberg , TJ . 2001 . Lactoferrin and cyclic lactoferricin inhibit the entry of human cytomegalovirus into human fibroblasts . Antiviral Res , 51 : 141 – 149 .
  • Anderson , BF , Baker , HM , Dodson , EJ , Norris , GE , Rumball , SV , Waters , JM and Baker , EN . 1987 . Structure of human lactoferrin at 3.2-A resolution . Proc Natl Acad Sci USA , 84 : 1769 – 1773 .
  • Appelmelk , BJ , An , YQ , Geerts , M , Thijs , BG , de Boer , HA , MacLaren , DM , de Graaff , J and Nuijens , JH . 1994 . Lactoferrin is a lipid A-binding protein . Infect Immun , 62 : 2628 – 2632 .
  • Archer , NK , Mazaitis , MJ , Costerton , JW , Leid , JG , Powers , ME and Shirtliff , ME . 2011 . Staphylococcus aureus biofilms: properties, regulation, and roles in human disease . Virulence , 2 : 445 – 459 .
  • Baker , HM and Baker , EN . 2012 . A structural perspective on lactoferrin function . Biochem Cell Biol , 90 : 320 – 328 .
  • Banin , E , Vasil , ML and Greenberg , EP . 2005 . Iron and Pseudomonas aeruginosa biofilm formation . Proc Natl Acad Sci USA , 102 : 11076 – 11081 .
  • Beasley , FC , Marolda , CL , Cheung , J , Buac , S and Heinrichs , DE . 2011 . Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by Staphyloferrin A, Staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence . Infect Immun , 79 : 2345 – 2355 .
  • Beenken , KE , Dunman , PM , McAleese , F , Macapagal , D , Murphy , E , Projan , SJ , Blevins , JS and Smeltzer , MS . 2004 . Global gene expression in Staphylococcus aureus biofilms . J Bacteriol , 186 : 4665 – 4684 .
  • Bellamy , W , Takase , M , Wakabayashi , H , Kawase , K and Tomita , M . 1992 . Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin . J Appl Bacteriol , 73 : 472 – 479 .
  • Bellamy , W , Takase , M , Yamauchi , K , Wakabayashi , H , Kawase , K and Tomita , M . 1992 . Identification of the bactericidal domain of lactoferrin . Biochem Biophys Acta , 1121 : 130 – 136 .
  • Bellamy , W , Wakabayashi , H , Takase , M , Kawase , K , Shimamura , S and Tomita , M . 1993 . Killing of Candida albicans by lactoferricin B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin . Med Microbiol Immunol , 182 : 97 – 105 .
  • Bjarnsholt , T , Kirketerp-Moller , K , Jensen , PO , Madsen , KG , Phipps , R , Krogfelt , K , Hoiby , N and Givskov , M . 2008 . Why chronic wounds will not heal: a novel hypothesis . Wound Repair Regen , 16 : 2 – 10 .
  • Bolscher , J , Nazmi , K , van Marle , J , van’t Hof , W and Veerman , E . 2012 . Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates the killing activity against Candida albicans . Biochem Cell Biol , 90 : 378 – 388 .
  • Booth , SC , Workentine , ML , Wen , J , Shaykhutdinov , R , Vogel , HJ , Ceri , H , Turner , RJ and Weljie , AM . 2011 . Differences in metabolism between the biofilm and planktonic response to metal stress . J Proteome Res , 10 : 3190 – 3199 .
  • Boucher , HW , Talbot , GH , Bradley , JS , Edwards , JE , Gilbert , D , Rice , LB , Scheld , M , Spellberg , B and Bartlett , J . 2009 . Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America . Clin Infect Dis , 48 : 1 – 12 .
  • Bowden , GH and Li , YH . 1997 . Nutritional influences on biofilm development . Adv Dent Res , 11 : 81 – 99 .
  • Brock , J . 1995 . Lactoferrin: a multifunctional immunoregulatory protein? . Immunol Today , 16 : 417 – 419 .
  • Brouwer , CP , Rahman , M and Welling , MM . 2011 . Discovery and development of a synthetic peptide derived from lactoferrin for clinical use . Peptides , 32 : 1953 – 1963 .
  • Brouwer , CP , Wulferink , M and Welling , MM . 2008 . The pharmacology of radiolabeled cationic antimicrobial peptides . J Pharm Sci , 97 : 1633 – 1651 .
  • Carlson , RP . 2007 . Metabolic systems cost-benefit analysis for interpreting network structure and regulation . Bioinformatics , 23 : 1258 – 1264 .
  • Carlson , RP . 2009 . Decomposition of complex microbial behaviors into resource-based stress responses . Bioinformatics , 25 : 90 – 97 .
  • Carlson , RP and Taffs , RL . 2010 . Molecular-level tradeoffs and metabolic adaptation to simultaneous stressors . Curr Opin Biotechnol , 21 : 670 – 676 .
  • Carpentier , B and Cerf , O . 1993 . Biofilms and their consequences, with particular reference to hygiene in the food industry . J Appl Bacteriol , 75 : 499 – 511 .
  • Chen , PW , Ho , SP , Shyu , CL and Mao , FC . 2004 . Effects of bovine lactoferrin hydrolysate on the in vitro antimicrobial susceptibility of Escherichia coli strains isolated from baby pigs . Am J Vet Res , 65 : 131 – 137 .
  • Cohen , MS , Mao , J , Rasmussen , GT , Serody , JS and Britigan , BE . 1992 . Interaction of lactoferrin and lipopolysaccharide (LPS): effects on the antioxidant property of lactoferrin and the ability of LPS to prime human neutrophils for enhanced superoxide formation . J Infect Dis , 166 : 1375 – 1378 .
  • Costerton , JW , Cheng , KJ , Geesey , GG , Ladd , TI , Nickel , JC , Dasgupta , M and Marrie , TJ . 1987 . Bacterial biofilms in nature and disease . Annu Rev Microbiol , 41 : 435 – 464 .
  • Costerton , JW , Stewart , PS and Greenberg , EP . 1999 . Bacterial biofilms: a common cause of persistent infections . Science , 284 : 1318 – 1322 .
  • Crosa , JH . 1989 . Genetics and molecular biology of siderophore-mediated iron transport in bacteria . Microbiol Rev , 53 : 517 – 530 .
  • Dathe , M and Wieprecht , T . 1999 . Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells . Biochim Biophys Acta , 1462 : 71 – 87 .
  • Davey , ME and O’Toole , GA . 2000 . Microbial biofilms: from ecology to molecular genetics . Microbiol Mol Biol Rev , 64 : 847 – 867 .
  • Davies , D . 2003 . Understanding biofilm resistance to antibacterial agents . Nat Rev Drug Discov , 2 : 114 – 122 .
  • Davis , SC , Ricotti , C , Cazzaniga , A , Welsh , E , Eaglstein , WH and Mertz , PM . 2008 . Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo . Wound Repair Regen , 16 : 23 – 29 .
  • de Araujo , AN and Giugliano , LG . 2001 . Lactoferrin and free secretory component of human milk inhibit the adhesion of enteropathogenic Escherichia coli to HeLa cells . BMC Microbiol , 1 : 25
  • de Oliveira , IR , de Araujo , AN , Bao , SN and Giugliano , LG . 2001 . Binding of lactoferrin and free secretory component to enterotoxigenic Escherichia coli . FEMS Microbiol Lett , 203 : 29 – 33 .
  • Donlan , RM . 2000 . Role of biofilms in antimicrobial resistance . ASAIO J , 46 : S47 – S52 .
  • Donlan , RM and Costerton , JW . 2002 . Biofilms: survival mechanisms of clinically relevant microorganisms . Clin Microbiol Rev , 15 : 167 – 193 .
  • Dunne , WM Jr . 2002 . Bacterial adhesion: seen any good biofilms lately? . Clin Microbiol Rev , 15 : 155 – 166 .
  • El Yazidi-Belkoura , I , Legrand , D , Nuijens , J , Slomianny , MC , van Berkel , P and Spik , G . 2001 . The binding of lactoferrin to glycosaminoglycans on enterocyte-like HT29-18-C1 cells is mediated through basic residues located in the N-terminus . Biochim Biophys Acta , 1568 : 197 – 204 .
  • Farnaud , S and Evans , RW . 2003 . Lactoferrin – a multifunctional protein with antimicrobial properties . Mol Immunol , 40 : 395 – 405 .
  • Fazli , M , Bjarnsholt , T , Kirketerp-Moller , K , Jorgensen , A , Andersen , CB , Givskov , M and Tolker-Nielsen , T . 2011 . Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds . Wound Repair Regen , 19 : 387 – 391 .
  • Fuchs , K , Deutz , A , Kofer , J , Wagner , P and Berg , W . 2007 . Analysis of the resistance behaviour of indicator bacteria to several antibiotics in bulk milk using spatial point pattern methodology . Vet Ital , 43 : 635 – 641 .
  • Fux , CA , Costerton , JW , Stewart , PS and Stoodley , P . 2005 . Survival strategies of infectious biofilms . Trends Microbiol , 13 : 34 – 40 .
  • Gemmel , F , Dumarey , N and Welling , M . 2009 . Future diagnostic agents . Semin Nucl Med , 39 : 11 – 26 .
  • Giugliano , LG , Ribeiro , ST , Vainstein , MH and Ulhoa , CJ . 1995 . Free secretory component and lactoferrin of human milk inhibit the adhesion of enterotoxigenic Escherichia coli . J Med Microbiol , 42 : 3 – 9 .
  • Gjersing , EL , Herberg , JL , Horn , J , Schaldach , CM and Maxwell , RS . 2007 . NMR metabolomics of planktonic and biofilm modes of growth in Pseudomonas aeruginosa . Anal Chem , 79 : 8037 – 8045 .
  • Gonzalez-Chavez , SA , Arevalo-Gallegos , S and Rascon-Cruz , Q . 2009 . Lactoferrin: structure, function and applications . Int J Antimicrob Agents , 33 : e301 – 308 .
  • Gordon , CA , Hodges , NA and Marriott , C . 1988 . Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa . J Antimicrob Chemother , 22 : 667 – 674 .
  • Gottrup , F . 2004 . A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds . Am J Surg , 187 : 38S – 43S .
  • Granstrom , TB , Izumori , K and Leisola , M . 2007 . A rare sugar xylitol. Part II: biotechnological production and future applications of xylitol . Appl Microbiol Biotechnol , 74 : 273 – 276 .
  • Grigg , JC , Cooper , JD , Cheung , J , Heinrichs , DE and Murphy , ME . 2010 . The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket . J Biol Chem , 285 : 11162 – 11171 .
  • Ha C, Kornbluth A. 2010. Mucosal healing in inflammatory bowel disease: where do we stand? Curr Gastroenterol Rep. 12:471–478.
  • Hajjar , AM , Ernst , RK , Tsai , JH , Wilson , CB and Miller , SI . 2002 . Human toll-like receptor 4 recognizes host-specific LPS modifications . Nat Immunol , 3 : 354 – 359 .
  • Haney , EF , Nazmi , K , Bolscher , JG and Vogel , HJ . 2012 . Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin . Biochim Biophys Acta , 1818 : 762 – 775 .
  • Harris , MR and Coote , PJ . 2010 . Combination of caspofungin or anidulafungin with antimicrobial peptides results in potent synergistic killing of Candida albicans and Candida glabrata in vitro . Int J Antimicrob Agents , 35 : 347 – 356 .
  • Harrison-Balestra , C , Cazzaniga , AL , Davis , SC and Mertz , PM . 2003 . A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours and is visualized by light microscopy . Dermatol Surg , 29 : 631 – 635 .
  • Hayssen , V . 1995 . Milk: it does a baby good . Natural History , 104 : 36
  • He , J and Furmanski , P . 1995 . Sequence specificity and transcriptional activation in the binding of lactoferrin to DNA . Nature , 373 : 721 – 724 .
  • Hu , W , Zhao , J , Wang , J , Yu , T , Wang , J and Li , N . 2012 . Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets . Biochem Cell Biol , 90 : 485 – 496 .
  • Hwang , PM , Zhou , N , Shan , X , Arrowsmith , CH and Vogel , HJ . 1998 . Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin . Biochemistry , 37 : 4288 – 4298 .
  • James , GA , Swogger , E , Wolcott , R , Pulcini , E , Secor , P , Sestrich , J , Costerton , JW and Stewart , PS . 2008 . Biofilms in chronic wounds . Wound Repair Regen , 16 : 37 – 44 .
  • Jones , EM , Smart , A , Bloomberg , G , Burgess , L and Millar , MR . 1994 . Lactoferricin, a new antimicrobial peptide . J Appl Bacteriol , 77 : 208 – 214 .
  • Jones , RN . 2001 . Resistance patterns among nosocomial pathogens: trends over the past few years . Chest , 119 ( Suppl ) : 397S – 404S .
  • Kaito , M , Iwasa , M , Fujita , N , Kobayashi , Y , Kojima , Y , Ikoma , J , Imoto , I , Adachi , Y , Hamano , H and Yamauchi , K . 2007 . Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin . J Gastroenterol Hepatol , 22 : 1894 – 1897 .
  • Kanyshkova , TG , Semenov , DV , Buneva , VN and Nevinsky , GA . 1999 . Human milk lactoferrin binds two DNA molecules with different affinities . FEBS Lett , 451 : 235 – 237 .
  • Kawasaki , Y , Tazume , S , Shimizu , K , Matsuzawa , H , Dosako , S , Isoda , H , Tsukiji , M , Fujimura , R , Muranaka , Y and Isihida , H . 2000 . Inhibitory effects of bovine lactoferrin on the adherence of enterotoxigenic Escherichia coli to host cells . Biosci Biotechnol Biochem , 64 : 348 – 354 .
  • Klein , G , Imreh , S and Zabarovsky , ER . 2007 . Why do we not all die of cancer at an early age? . Adv Cancer Res , 98 : 1 – 16 .
  • Klevens , RM , Edwards , JR , Richards , CL Jr. , Horan , TC , Gaynes , RP , Pollock , DA and Cardo , DM . 2007 . Estimating health care-associated infections and deaths in US hospitals, 2002 . Public Health Rep , 122 : 160 – 166 .
  • Kumon , H , Tomochika , K , Matunaga , T , Ogawa , M and Ohmori , H . 1994 . A sandwich cup method for the penetration assay of antimicrobial agents through Pseudomonas exopolysaccharides . Microbiol Immunol , 38 : 615 – 619 .
  • Kuwata , H , Yip , TT , Tomita , M and Hutchens , TW . 1998 . Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin . Biochim Biophys Acta , 1429 : 129 – 141 .
  • Lacasse , P , Lauzon , K , Diarra , MS and Petitclerc , D . 2008 . Utilization of lactoferrin to fight antibiotic-resistant mammary gland pathogens . J Anim Sci , 86 ( Suppl ) : 66 – 71 .
  • Lamont , IL , Martin , LW , Sims , T , Scott , A and Wallace , M . 2006 . Characterization of a gene encoding an acetylase required for pyoverdine synthesis in Pseudomonas aeruginosa . J Bacteriol , 188 : 3149 – 3152 .
  • Laverty , G , Gorman , SP and Gilmore , BF . 2011 . The potential of antimicrobial peptides as biocides . Int J Mol Sci , 12 : 6566 – 6596 .
  • Lawrence , JR , Korber , DR , Hoyle , BD , Costerton , JW and Caldwell , DE . 1991 . Optical sectioning of microbial biofilms . J Bacteriol , 173 : 6558 – 6567 .
  • Lesman-Movshovich , E , Lerrer , B and Gilboa-Garber , N . 2003 . Blocking of Pseudomonas aeruginosa lectins by human milk glycans . Can J Microbiol , 49 : 230 – 235 .
  • Lewis , K . 2001 . Riddle of biofilm resistance . Antimicrob Agents Chemother , 45 : 999 – 1007 .
  • Licking , E . 1999 . Getting a grip on bacterial slime . Business Week , 13 : 98 – 100 .
  • Ling , JM and Schryvers , AB . 2006 . Perspectives on interactions between lactoferrin and bacteria . Biochem Cell Biol , 84 : 275 – 281 .
  • Lupetti , A , Paulusma-Annema , A , Welling , MM , Dogterom-Ballering , H , Brouwer , CP , Senesi , S , Van Dissel , JT and Nibbering , PH . 2003 . Synergistic activity of the N-terminal peptide of human lactoferrin and fluconazole against Candida species . Antimicrob Agents Chemother , 47 : 262 – 267 .
  • Mah , TF , Pitts , B , Pellock , B , Walker , GC , Stewart , PS and O’Toole , GA . 2003 . A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance . Nature , 426 : 306 – 310 .
  • Malmquist , J , Thorell , JI and Wolheim , FA . 1977 . Lactoferrin and lysozyme in arthritic exudates . Acta Med Scand , 202 : 313 – 318 .
  • Mariller , C , Hardiville , S , Hoedt , E , Huvent , I , Pina-Canseco , S and Pierce , A . 2012 . Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor . Biochem Cell Biol , 90 : 307 – 319 .
  • Masson , PL , Heremans , JF and Schonne , E . 1969 . Lactoferrin, an iron-binding protein in neutrophilic leukocytes . J Exp Med , 130 : 643 – 658 .
  • 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 .
  • McGuckin M, Goldman R, Bolton L, Salcido R. 2003. The clinical relevance of microbiology in acute and chronic wounds. Adv Skin Wound Care. 16:12–23; quiz 24–15.
  • Miethke , M and Marahiel , MA . 2007 . Siderophore-based iron acquisition and pathogen control . Microbiol Mol Biol Rev , 71 : 413 – 451 .
  • Naidu , AS , Fowler , RS , Martinez , C , Chen , J and Tulpinski , J . 2004 . Activated lactoferrin and fluconazole synergism against Candida albicans and Candida glabrata vaginal isolates . J Reprod Med , 49 : 800 – 807 .
  • Neilands , JB . 1981a . Microbial iron compounds . Annu Rev Biochem , 50 : 715 – 731 .
  • Neilands , JB . 1981b . Iron absorption and transport in microorganisms . Annu Rev Nutr , 1 : 27 – 46 .
  • Neilands , JB . 1995 . Siderophores: structure and function of microbial iron transport compounds . J Biol Chem , 270 : 26723 – 26726 .
  • Ochoa , TJ , Chea-Woo , E , Campos , M , Pecho , I , Prada , A , McMahon , RJ and Cleary , TG . 2008 . Impact of lactoferrin supplementation on growth and prevalence of Giardia colonization in children . Clin Infect Dis , 46 : 1881 – 1883 .
  • Ochoa , TJ , Noguera-Obenza , M , Ebel , F , Guzman , CA , Gomez , HF and Cleary , TG . 2003 . Lactoferrin impairs type III secretory system function in enteropathogenic Escherichia coli . Infect Immun , 71 : 5149 – 5155 .
  • Ochoa , TJ , Pezo , A , Cruz , K , Chea-Woo , E and Cleary , TG . 2012 . Clinical studies of lactoferrin in children . Biochem Cell Biol , 90 : 457 – 467 .
  • Oseas , R , Yang , HH , Baehner , RL and Boxer , LA . 1981 . Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness . Blood , 57 : 939 – 945 .
  • Park , JH , Park , GT , Cho , IH , Sim , SM , Yang , JM and Lee , DY . 2011 . An antimicrobial protein, lactoferrin exists in the sweat: proteomic analysis of sweat . Exp Dermatol , 20 : 369 – 371 .
  • Parsek , MR and Singh , PK . 2003 . Bacterial biofilms: an emerging link to disease pathogenesis . Annu Rev Microbiol , 57 : 677 – 701 .
  • Peleg , AY and Hooper , DC . 2010 . Hospital-acquired infections due to gram-negative bacteria . N Engl J Med , 362 : 1804 – 1813 .
  • Poole , K , Neshat , S , Krebes , K and Heinrichs , DE . 1993 . Cloning and nucleotide sequence analysis of the ferripyoverdine receptor gene fpvA of Pseudomonas aeruginosa . J Bacteriol , 175 : 4597 – 4604 .
  • Redly , GA and Poole , K . 2005 . FpvIR control of fpvA ferric pyoverdine receptor gene expression in Pseudomonas aeruginosa: demonstration of an interaction between FpvI and FpvR and identification of mutations in each compromising this interaction . J Bacteriol , 187 : 5648 – 5657 .
  • Resch , A , Leicht , S , Saric , M , Pasztor , L , Jakob , A , Gotz , F and Nordheim , A . 2006 . Comparative proteome analysis of Staphylococcus aureus biofilm and planktonic cells and correlation with transcriptome profiling . Proteomics , 6 : 1867 – 1877 .
  • Resch , A , Rosenstein , R , Nerz , C and Gotz , F . 2005 . Differential gene expression profiling of Staphylococcus aureus cultivated under biofilm and planktonic conditions . Appl Environ Microbiol , 71 : 2663 – 2676 .
  • Sanchez , MS and Watts , JL . 1999 . Enhancement of the activity of novobiocin against Escherichia coli by lactoferrin . J Dairy Sci , 82 : 494 – 499 .
  • Saponja , JA and Vogel , HJ . 1996 . Metal-ion binding properties of the transferrins: a vanadium-51 NMR study . J Inorg Biochem , 62 : 253 – 270 .
  • Siebert PD, Huang BC. 1997. Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines. Proc Natl Acad Sci USA. 94: 2198–2203.
  • Singh , PK , Parsek , MR , Greenberg , EP and Welsh , MJ . 2002 . A component of innate immunity prevents bacterial biofilm development . Nature , 417 : 552 – 555 .
  • Sitaram , N . 2006 . Antimicrobial peptides with unusual amino acid compositions and unusual structures . Curr Med Chem , 13 : 679 – 696 .
  • Stewart , JA , Silimperi , D , Harris , P , Wise , NK , Fraker , TD and Kisslo , JA . 1980 . Echocardiographic documentation of vegetative lesions in infective endocarditis: clinical implications . Circulation , 61 : 374 – 380 .
  • Stewart , PS and Franklin , MJ . 2008 . Physiological heterogeneity in biofilms . Nat Rev Microbiol , 6 : 199 – 210 .
  • Stoodley , P , Cargo , R , Rupp , CJ , Wilson , S and Klapper , I . 2002 . Biofilm material properties as related to shear-induced deformation and detachment phenomena . J Ind Microbiol Biotechnol , 29 : 361 – 367 .
  • Strom , MB , Haug , BE , Rekdal , O , Skar , ML , Stensen , W and Svendsen , JS . 2002 . Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity . Biochem Cell Biol , 80 : 65 – 74 .
  • Suzuki , YA , Lopez , V and Lonnerdal , B . 2005 . Mammalian lactoferrin receptors: structure and function . Cell Mol Life Sci , 62 : 2560 – 2575 .
  • Valenti , P , Berlutti , F , Conte , MP , Longhi , C and Seganti , L . 2004 . Lactoferrin functions: current status and perspectives . J Clin Gastroenterol , 38 ( Suppl ) : S127 – S129 .
  • Valenti , P , Greco , R , Pitari , G , Rossi , P , Ajello , M , Melino , G and Antonini , G . 1999 . Apoptosis of Caco-2 intestinal cells invaded by Listeria monocytogenes: protective effect of lactoferrin . Exp Cell Res , 250 : 197 – 202 .
  • van der Kraan , MI , Groenink , J , Nazmi , K , Veerman , EC , Bolscher , JG and Nieuw Amerongen , AV . 2004 . Lactoferrampin: a novel antimicrobial peptide in the N1-domain of bovine lactoferrin . Peptides , 25 : 177 – 183 .
  • van der Kraan , MI , Nazmi , K , Teeken , A , Groenink , J , van’t Hof , W , Veerman , EC , Bolscher , JG and Nieuw Amerongen , AV . 2005 . Lactoferrampin, an antimicrobial peptide of bovine lactoferrin, exerts its candidacidal activity by a cluster of positively charged residues at the C-terminus in combination with a helix-facilitating N-terminal part . Biol Chem , 386 : 137 – 142 .
  • Venkatesh , MP and Rong , L . 2008 . Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis . J Med Microbiol , 57 : 1113 – 1121 .
  • Vettoretti , L , Plesiat , P , Muller , C , El Garch , F , Phan , G , Attree , I , Ducruix , A and Llanes , C . 2009 . Efflux unbalance in Pseudomonas aeruginosa isolates from cystic fibrosis patients . Antimicrob Agents Chemother , 53 : 1987 – 1997 .
  • Wakabayashi , H , Abe , S , Okutomi , T , Tansho , S , Kawase , K and Yamaguchi , H . 1996 . Cooperative anti-Candida effects of lactoferrin or its peptides in combination with azole antifungal agents . Microbiol Immunol , 40 : 821 – 825 .
  • Wakabayashi , H , Matsumoto , H , Hashimoto , K , Teraguchi , S , Takase , M and Hayasawa , H . 1999 . N-Acylated and D enantiomer derivatives of a nonamer core peptide of lactoferricin B showing improved antimicrobial activity . Antimicrob Agents Chemother , 43 : 1267 – 1269 .
  • Wakabayashi , H , Takase , M and Tomita , M . 2003 . Lactoferricin derived from milk protein lactoferrin . Curr Pharm Des , 9 : 1277 – 1287 .
  • Welling , MM , Paulusma-Annema , A , Balter , HS , Pauwels , EK and Nibbering , PH . 2000 . Technetium-99m labelled antimicrobial peptides discriminate between bacterial infections and sterile inflammations . Eur J Nucl Med , 27 : 292 – 301 .
  • Wild , S , Roglic , G , Green , A , Sicree , R and King , H . 2004 . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 . Diabetes Care , 27 : 1047 – 1053 .
  • Wilderman , PJ , Vasil , AI , Johnson , Z , Wilson , MJ , Cunliffe , HE , Lamont , IL and Vasil , ML . 2001 . Characterization of an endoprotease (PrpL) encoded by a PvdS-regulated gene in Pseudomonas aeruginosa . Infect Immun , 69 : 5385 – 5394 .
  • Wolcott RD, Rhoads DD. 2008. A study of biofilm-based wound management in subjects with critical limb ischaemia. J Wound Care. 17:145–148, 150–142, 154–145.
  • Xiao , R and Kisaalita , WS . 1997 . Iron acquisition from transferrin and lactoferrin by Pseudomonas aeruginosa pyoverdin . Microbiology , 143 : 2509 – 2515 .
  • Yamauchi , K , Tomita , M , Giehl , TJ and Ellison , RT 3rd . 1993 . Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment . Infect Immun , 61 : 719 – 728 .
  • Yen , CC , Shen , CJ , Hsu , WH , Chang , YH , Lin , HT , Chen , HL and Chen , CM . 2011 . Lactoferrin: an iron-binding antimicrobial protein against Escherichia coli infection . Biometals , 24 : 585 – 594 .
  • Zagulski , T , Lipinski , P , Zagulska , A and Jarzabek , Z . 1998 . Antibacterial system generated by lactoferrin in mice in vivo is primarily a killing system . Int J Exp Pathol , 79 : 117 – 123 .
  • Zasloff , M . 2002 . Antimicrobial peptides of multicellular organisms . Nature , 415 : 389 – 395 .
  • Zhu , Y , Weiss , EC , Otto , M , Fey , PD , Smeltzer , MS and Somerville , GA . 2007 . Staphylococcus aureus biofilm metabolism and the influence of arginine on polysaccharide intercellular adhesin synthesis, biofilm formation, and pathogenesis . Infect Immun , 75 : 4219 – 4226 .
  • Zullo , A , De Francesco , V , Scaccianoce , G , Manes , G , Efrati , C , Hassan , C , Maconi , G , Piglionica , D , Cannaviello , C Panella , C . 2007 . Helicobacter pylori eradication with either quadruple regimen with lactoferrin or levofloxacin-based triple therapy: a multicentre study . Digest Liver Dis , 39 : 806 – 810 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.