Influence of Amphibian Antimicrobial Peptides and Short Lipopeptides on Bacterial Biofilms Formed on Contact Lenses

The widespread use of contact lenses is associated with several complications, including ocular biofilm-related infections. They are very difficult to manage with standard antimicrobial therapies, because bacterial growth in a biofilm is associated with an increased antibiotic resistance. The principal aim of this study was to evaluate the efficacy of antimicrobial peptides (AMPs) in eradication of bacterial biofilms formed on commercially available contact lenses. AMPs were synthesized according to Fmoc/tBu chemistry using the solid-phase method. Minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of the compounds were determined. Anti-biofilm activity of the antimicrobial peptides determined at different temperatures (25 °C and 37 °C) were compared with the effectiveness of commercially available contact lens solutions. All of the tested compounds exhibited stronger anti-biofilm properties as compared to those of the tested lens solutions. The strongest activity of AMPs was noticed against Gram-positive strains at a temperature of 25 °C. Conclusions: The results of our experiments encourage us toward further studies on AMPs and their potential application in the prophylaxis of contact lens-related eye infections.

[1]  L. Thornell,et al.  A Qualitative Test for Monitoring Coupling Completeness in Solid Phase Peptide Synthesis Using Chloranil. , 1979 .

[2]  G. O’Toole,et al.  Mechanisms of biofilm resistance to antimicrobial agents. , 2001, Trends in microbiology.

[3]  P. Trzonkowski,et al.  Safety profile of antimicrobial peptides: camel, citropin, protegrin, temporin a and lipopeptide on HaCaT keratinocytes. , 2013, Acta poloniae pharmaceutica.

[4]  M. Ghannoum,et al.  Fusarium and Candida albicans Biofilms on Soft Contact Lenses: Model Development, Influence of Lens Type, and Susceptibility to Lens Care Solutions , 2007, Antimicrobial Agents and Chemotherapy.

[5]  M. Willcox,et al.  Biocompatibility of Antimicrobial Melimine Lenses: Rabbit and Human Studies , 2014, Optometry and vision science : official publication of the American Academy of Optometry.

[6]  T. Williams,et al.  Bacterial interactions with contact lenses; effects of lens material, lens wear and microbial physiology. , 2001, Biomaterials.

[7]  M. Okrój,et al.  In Vitro Activities of the Lipopeptides Palmitoyl (Pal)-Lys-Lys-NH2 and Pal-Lys-Lys Alone and in Combination with Antimicrobial Agents against Multiresistant Gram-Positive Cocci , 2006, Antimicrobial Agents and Chemotherapy.

[8]  L. Keay,et al.  Epidemiology of Contact Lens–Related Inflammation and Microbial Keratitis: A 20-year Perspective , 2007, Eye & contact lens.

[9]  J. Bertino,et al.  Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics , 2009, Clinical ophthalmology.

[10]  M. Provinciali,et al.  Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis , 2016, Shock.

[11]  W. Maloy,et al.  Structure–activity studies on magainins and other host defense peptides , 1995, Biopolymers.

[12]  F. Paulsen,et al.  Expression and regulation of antimicrobial peptide psoriasin (S100A7) at the ocular surface and in the lacrimal apparatus. , 2011, Investigative ophthalmology & visual science.

[13]  P. Sankaridurg,et al.  In vivo performance of melimine as an antimicrobial coating for contact lenses in models of CLARE and CLPU. , 2009, Investigative ophthalmology & visual science.

[14]  B. Weissman,et al.  Why daily wear is still better than extended wear. , 2003, Eye & contact lens.

[15]  L. Szczotka-Flynn,et al.  Risk factors for corneal infiltrative events during continuous wear of silicone hydrogel contact lenses. , 2010, Investigative ophthalmology & visual science.

[16]  B. Jansen,et al.  Infections associated with medical devices: pathogenesis, management and prophylaxis. , 2005, Drugs.

[17]  L. Szczotka-Flynn,et al.  Risk Factors for Contact Lens Bacterial Contamination During Continuous Wear , 2009, Optometry and vision science : official publication of the American Academy of Optometry.

[18]  Robert E. W. Hancock,et al.  Multilayered coating on titanium for controlled release of antimicrobial peptides for the prevention of implant-associated infections. , 2013, Biomaterials.

[19]  T. Morris,et al.  Monitoring antibiotic resistance in ocular microorganisms: results from the Antibiotic Resistance Monitoring in Ocular micRorganisms (ARMOR) 2009 surveillance study. , 2011, American journal of ophthalmology.

[20]  W. Kamysz,et al.  The Antistaphylococcal Activity of Citropin 1.1 and Temporin A against Planktonic Cells and Biofilms Formed by Isolates from Patients with Atopic Dermatitis: An Assessment of Their Potential to Induce Microbial Resistance Compared to Conventional Antimicrobials , 2016, Pharmaceuticals.

[21]  T. Gray,et al.  Acanthamoeba, bacterial, and fungal contamination of contact lens storage cases. , 1995, The British journal of ophthalmology.

[22]  C. Murphy,et al.  In Vitro Antimicrobial Activity of Shiva-11 Against Ocular Pathogens , 1994, Cornea.

[23]  N. Kumar,et al.  A novel cationic‐peptide coating for the prevention of microbial colonization on contact lenses , 2008, Journal of applied microbiology.

[24]  Wojciech Kamysz,et al.  Activity of short lipopeptides and conventional antimicrobials against planktonic cells and biofilms formed by clinical strains of Staphylococcus aureus. , 2012, Future medicinal chemistry.

[25]  U. Römling,et al.  Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation of Staphylococcus epidermidis , 2010, Letters in applied microbiology.

[26]  B. Holden,et al.  Contact Lens Related Corneal Infections , 2001, Bioscience reports.

[27]  W. Kamysz,et al.  Activity of Antimicrobial Peptides and Conventional Antibiotics against Superantigen Positive Staphylococcus aureus Isolated from the Patients with Neoplastic and Inflammatory Erythrodermia , 2011, Chemotherapy research and practice.

[28]  W. Kamysz,et al.  The lipopeptides Pal–Lys–Lys–NH2 and Pal–Lys–Lys soaking alone and in combination with intraperitoneal vancomycin prevent vascular graft biofilm in a subcutaneous rat pouch model of staphylococcal infection , 2007, Peptides.

[29]  M. Rocchi,et al.  Temporin A Soaking in Combination with Intraperitoneal Linezolid Prevents Vascular Graft Infection in a Subcutaneous Rat Pouch Model of Infection with Staphylococcus epidermidis with Intermediate Resistance to Glycopeptides , 2004, Antimicrobial Agents and Chemotherapy.

[30]  D. Andreu,et al.  Effect of hybrid peptides of cecropin A and melittin in an experimental model of bacterial keratitis. , 1997, Cornea.

[31]  A. McDermott,et al.  Role of host-defence peptides in eye diseases , 2011, Cellular and Molecular Life Sciences.

[32]  J. Łukasiak,et al.  Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides , 2003, Circulation.

[33]  A. McDermott.  Defensins and other antimicrobial peptides at the ocular surface. , 2004, The ocular surface.

[34]  J. Łukasiak,et al.  Temporin A alone and in combination with imipenem reduces lethality in a mouse model of staphylococcal sepsis. , 2005, Journal of Infectious Diseases.

[35]  L. Wilson,et al.  Microbial contamination of contact lens storage cases and solutions. , 1990, American journal of ophthalmology.

[36]  A. McDermott.  The Role of Antimicrobial Peptides at the Ocular Surface , 2008, Ophthalmic Research.

[37]  W. Kamysz,et al.  Temporin A is effective in MRSA-infected wounds through bactericidal activity and acceleration of wound repair in a murine model , 2008, Peptides.

[38]  L. Szczotka-Flynn,et al.  Predictive factors for corneal infiltrates with continuous wear of silicone hydrogel contact lenses. , 2007, Archives of ophthalmology.

[39]  M. Willcox,et al.  Broad spectrum antimicrobial activity of melimine covalently bound to contact lenses. , 2013, Investigative ophthalmology & visual science.

[40]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[41]  Krishna Kumar,et al.  Antimicrobial activity and protease stability of peptides containing fluorinated amino acids. , 2007, Journal of the American Chemical Society.

[42]  G. Fields,et al.  Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. , 2009, International journal of peptide and protein research.

[43]  M. Willcox,et al.  Elucidation of the antistaphylococcal action of lactoferrin and lysozyme. , 1999, Journal of medical microbiology.

[44]  F. Stapleton,et al.  The Causes of and Cures for Contact Lens-Induced Peripheral Ulcer , 2003, Eye & contact lens.

[45]  N. Khardori,et al.  Biofilms in device-related infections , 1995, Journal of Industrial Microbiology.

[46]  M. Amiri,et al.  Contact lens disinfecting solutions antibacterial efficacy: comparison between clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus , 2012, Eye.

[47]  W. Kamysz,et al.  Determination of counter‐ions in synthetic peptides by ion chromatography, capillary isotachophoresis and capillary electrophoresis , 2012, Journal of peptide science : an official publication of the European Peptide Society.

[48]  C. Gunderson,et al.  Efficacy of Contact Lens Disinfecting Solutions Against Staphylococcus aureus and Pseudomonas aeruginosa , 2006, Eye & contact lens.

[49]  M. Willcox,et al.  Factors influencing bacterial adhesion to contact lenses , 2012, Molecular vision.

[50]  M. Campa,et al.  Use of antimicrobial peptides against microbial biofilms: advantages and limits. , 2011, Current medicinal chemistry.

[51]  A. Ramamoorthy,et al.  Antimicrobial activity and membrane selective interactions of a synthetic lipopeptide MSI-843. , 2005, Biochimica et biophysica acta.

[52]  Antimicrobial peptides as potential tool to fight bacterial biofilm. , 2014, Acta poloniae pharmaceutica.

[53]  I. Kilpeläinen,et al.  Antibacterial activities of temporin A analogs , 2000, FEBS letters.

[54]  D. Barra,et al.  Temporins, antimicrobial peptides from the European red frog Rana temporaria. , 1996, European journal of biochemistry.

[55]  J. Stein,et al.  Compliance and Contact Lens Care: A New Assessment Method , 1993, Optometry and vision science : official publication of the American Academy of Optometry.

[56]  Mahmoud Ghannoum,et al.  Microbial Contamination of Contact Lenses, Lens Care Solutions, and Their Accessories: A Literature Review , 2010, Eye & contact lens.

[57]  M. Willcox.  Review of resistance of ocular isolates of Pseudomonas aeruginosa and staphylococci from keratitis to ciprofloxacin, gentamicin and cephalosporins , 2011, Clinical & experimental optometry.

[58]  A. McDermott.  Antimicrobial compounds in tears. , 2013, Experimental eye research.

[59]  L. Bevanger,et al.  Microbial contamination of contact lens cases among medical students. , 1996, The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists, Inc.

[60]  M. Okrój,et al.  Temporin A and its retro‐analogues: synthesis, conformational analysis and antimicrobial activities , 2006, Journal of peptide science : an official publication of the European Peptide Society.

[61]  I. Radzishevsky,et al.  Effects of Acyl versus Aminoacyl Conjugation on the Properties of Antimicrobial Peptides , 2005, Antimicrobial Agents and Chemotherapy.

[62]  R. Kolter,et al.  Biofilm formation as microbial development. , 2000, Annual review of microbiology.

[63]  J. Carver,et al.  Host defence peptides from the skin glands of the Australian blue mountains tree-frog Litoria citropa. Solution structure of the antibacterial peptide citropin 1.1. , 1999, European journal of biochemistry.

[64]  E. Hume,et al.  Soft Contact Lens Disinfection Solution Efficacy: Clinical Fusarium Isolates vs. ATCC 36031 , 2009, Optometry and vision science : official publication of the American Academy of Optometry.

[65]  Ronald N. Jones,et al.  In vitro spectrum of pexiganan activity; bactericidal action and resistance selection tested against pathogens with elevated MIC values to topical agents. , 2016, Diagnostic microbiology and infectious disease.

[66]  J. Łukasiak,et al.  Citropin 1.1-treated central venous catheters improve the efficacy of hydrophobic antibiotics in the treatment of experimental staphylococcal catheter-related infection , 2006, Peptides.

[67]  Wayne L. Smith,et al.  The use of synthetic Cecropin (D5C) in disinfecting contact lens solutions. , 1996, The CLAO journal : official publication of the Contact Lens Association of Ophthalmologists, Inc.

[68]  Shirley Lam,et al.  Efficacy of Contact Lens Multipurpose Solutions Against Serratia Marcescens , 2007, Optometry and Vision Science.