Effects of carbohydrate polymers applicable in saliva substitutes on the anti-Candida activity of a histatin-derived peptide.

The effects of polymers applicable in saliva substitutes on the anti-Candida activity of the cationic antimicrobial peptide dhvar1 were investigated. Dhvar1 is a derivative of the 14 C-terminal amino acids of histatin 5. The effects of the following polymers were tested: uncharged hydroxyethylcellulose (HEC), negatively charged xanthan (XG) and three types of negatively charged carboxymethylcellulose (CMC) of identical mass but different degrees of carboxylic acid-group substitution (DS). The effects were tested at pH 4.0, 7.0 and 8.5 in a killing assay. HEC had no effect at any pH tested; XG and the three types of CMC caused a decrease in activity at increasing concentrations. Within the CMC group, inhibition increased slightly with increasing DS. These results suggest that the reduction in activity associated with these polymers is the result of electrostatic interaction between the positively charged peptides and the negatively charged polymers. In the absence of polymers, no effect of pH was found on the activity of dhvar1. In the presence of the charged polymers XG and CMC, lowering the pH from 7.0 to 4.0 resulted in a decrease of dhvar1 activity. It was concluded that, with respect to the retention of activity, HEC is the most appropriate polymer for use in combination with dhvar1. However, for use in saliva substitutes XG seems more suitable because of its rheological properties. If XG or CMC are to be used, their reductive effect on the anti-Candida activity of dhvar1 should be compensated for by increasing the peptide dose.

[1]  S. Amyes,et al.  Sequence Analysis of ARI-1, a Novel OXA β-Lactamase, Responsible for Imipenem Resistance inAcinetobacter baumannii 6B92 , 2000, Antimicrobial Agents and Chemotherapy.

[2]  Gregory A.Petsko and Dagmar Ringe.  Protein structure and function , 2003 .

[3]  P. Barkvoll,et al.  Clinical Implications of the Dry Mouth: Oral Mucosal Diseases , 1998, Annals of the New York Academy of Sciences.

[4]  D. Landman,et al.  Failure of all antifungal therapy for infection due to Candida albicans: a new AIDS-related problem? , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  M. Jensen,et al.  Comparison of Methods for Monitoring Changes in the pH of Human Dental Plaque , 1982, Journal of dental research.

[6]  C. Tylenda,et al.  Antifungal activities of salivary histidine-rich polypeptides against Candida albicans and other oral yeast isolates. , 1992, Oral microbiology and immunology.

[7]  V. Iacono,et al.  Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans , 1984, Infection and immunity.

[8]  R. Gennaro,et al.  Rapid membrane permeabilization and inhibition of vital functions of gram-negative bacteria by bactenecins , 1990, Infection and immunity.

[9]  J. Wingard,et al.  Isolation and characterization of fluconazole- and amphotericin B-resistant Candida albicans from blood of two patients with leukemia , 1997, Antimicrobial agents and chemotherapy.

[10]  Arie V. Nieuw Amerongen,et al.  Antimicrobial Peptides: Properties and Applicability , 2001, Biological chemistry.

[11]  R I Lehrer,et al.  Antimicrobial peptides in mammalian and insect host defence. , 1999, Current opinion in immunology.

[12]  E. Veerman,et al.  Effects of histatin 5 and derived peptides on Candida albicans. , 2001, The Biochemical journal.

[13]  E. Veerman,et al.  A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides , 1999, FEBS letters.

[14]  P. A. Raj,et al.  Salivary histatin 5: dependence of sequence, chain length, and helical conformation for candidacidal activity. , 1990, The Journal of biological chemistry.

[15]  E. Veerman,et al.  Amphotericin B- and Fluconazole-ResistantCandida spp., Aspergillus fumigatus, and Other Newly Emerging Pathogenic Fungi Are Susceptible to Basic Antifungal Peptides , 1999, Antimicrobial Agents and Chemotherapy.

[16]  R. Eng,et al.  Development of resistance in candida isolates from patients receiving prolonged antifungal therapy , 1991, Antimicrobial Agents and Chemotherapy.

[17]  J. M. Nauta,et al.  Efficacy of a synthetic polymer saliva substitute in reducing oral complaints of patients suffering from irradiation-induced xerostomia. , 1998, Quintessence international.

[18]  H. Junginger.  BIOADHESIVE POLYMER SYSTEMS FOR PEPTIDE DELIVERY , 1990 .

[19]  J. Beeley,et al.  Natural and synthetic saliva: a stimulating subject. , 1994, Biotechnology & Genetic Engineering Reviews.

[20]  T. C. White,et al.  Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance , 1998, Clinical Microbiology Reviews.

[21]  H. G. Boman,et al.  Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine , 1993, Infection and immunity.

[22]  E. Veerman,et al.  Evaluation of the use of xanthan as vehicle for cationic antifungal peptides. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[23]  T. Abee,et al.  The Cellular Target of Histatin 5 on Candida albicans Is the Energized Mitochondrion* , 1999, The Journal of Biological Chemistry.

[24]  M. Larsen,et al.  Individual variations of pH, buffer capacity, and concentrations of calcium and phosphate in unstimulated whole saliva. , 1999, Archives of oral biology.

[25]  D. Pettitt,et al.  XANTHAN, GELLAN, WELAN, AND RHAMSAN , 1993 .

[26]  A. Vissink,et al.  Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjögren's syndrome. , 1996, Arthritis and rheumatism.

[27]  A. Vissink,et al.  Rheological properties of saliva substitutes containing mucin, carboxymethylcellulose or polyethylenoxide. , 1984, Journal of oral pathology.

[28]  W. A. van der Reijden,et al.  Shear rate dependent viscoelastic behavior of human glandular salivas. , 1993, Biorheology.

[29]  F C Kafatos,et al.  Phylogenetic perspectives in innate immunity. , 1999, Science.

[30]  H. C. van der Mei,et al.  Adhesion to silicone rubber of yeasts and bacteria isolated from voice prostheses: influence of salivary conditioning films. , 1997, Journal of biomedical materials research.

[31]  R. Houghten,et al.  The Role of Amphipathicity in the Folding, Self-association and Biological Activity of Multiple Subunit Small Proteins (*) , 1995, The Journal of Biological Chemistry.

[32]  E. Veerman,et al.  Synthetic histatin analogues with broad-spectrum antimicrobial activity. , 1997, The Biochemical journal.

[33]  A. Desmarais,et al.  CHAPTER 19 – HYDROXYALKYL AND ETHYL ETHERS OF CELLULOSE , 1993 .

[34]  Y. Shai,et al.  Mode of action of linear amphipathic α-helical antimicrobial peptides , 1998 .

[35]  H. G. Boman,et al.  Gene‐Encoded Peptide Antibiotics and the Concept of Innate Immunity: An Update Review , 1998, Scandinavian journal of immunology.

[36]  C. B. Park,et al.  Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. , 1998, Biochemical and biophysical research communications.

[37]  M. van den Berg,et al.  Epitope mapping of the Dermatophagoides pteronyssinus house dust mite major allergen Der p II using overlapping synthetic peptides. , 1991, Molecular immunology.

[38]  E. Veerman,et al.  Synergistic effects of low doses of histatin 5 and its analogues on amphotericin B anti-mycotic activity , 2000, Antonie van Leeuwenhoek.

[39]  C. B. Park,et al.  A novel antimicrobial peptide from Bufo bufo gargarizans. , 1996, Biochemical and biophysical research communications.

[40]  M. Klepser,et al.  Update on antifungal resistance. , 1997, Trends in microbiology.

[41]  J. Conly,et al.  Disseminated candidiasis due to amphotericin B-resistant Candida albicans. , 1992, The Journal of infectious diseases.