Effect of donor age on the concentrations of histatins in human parotid and submandibular/sublingual saliva

Histatins are a group of antimicrobial peptides, found in the saliva of man and some higher primates, which possess antifungal properties. Histatins bind to a receptor on the fungal cell membrane and enter the cytoplasm where they target the mitochondrion. They induce the non-lytic loss of ATP from actively respiring cells, which can induce cell death. In addition, they have been shown to disrupt the cell cycle and lead to the generation of reactive oxygen species. Their mode of action is distinct from those exhibited by the conventional azole and polyene drugs, hence histatins may have applications in controlling drug-resistant fungal infections. The possibility of utilising histatins for the control of fungal infections of the oral cavity is being actively pursued with the antifungal properties of topical histatin preparations and histatin-impregnated denture acrylic being evaluated. Initial clinical studies are encouraging, having demonstrated the safety and efficacy of histatin preparations in blocking the adherence of the yeast Candida albicans to denture acrylic, retarding plaque formation and reducing the severity of gingivitis. Histatins may represent a new generation of antimicrobial compounds for the treatment of oral fungal infections and have the advantage, compared with conventional antifungal agents, of being a normal component of human saliva with no apparent adverse effects on host tissues and having a mode of action distinct to azole and polyene antifungals.

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“…In contrast, however, the production of histatins decreases with age, as the incidence of oral fungal infection rises (Johnson et al 2000).…”

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confidence: 96%

Histatins: antimicrobial peptides with therapeutic potential

Kavanagh

Dowd

2004

Journal of Pharmacy and Pharmacology

167

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“…Major interest in histatins stems from the fact that they exhibit cidal activities against a broad range of pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus (1,(3)(4)(5). In view of this in vitro activity and the relative abundance of histatins in parotid and submandibular͞sublingual secretions (6), these proteins may represent major components of the nonimmune host defense system involved in the maintenance of oral health.…”

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confidence: 99%

The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species

Helmerhorst

Troxler

Oppenheim

2001

Proc. Natl. Acad. Sci. U.S.A.

209

160

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Previous studies have shown that the human salivary antifungal peptide histatin 5 is taken up by Candida albicans cells and associates intracellularly with mitochondria. The purpose of the present study was to investigate the biological consequence of this specific subcellular targeting. Histatin 5 inhibited respiration of isolated C. albicans mitochondria as well as the respiration of intact blastoconidia in a dose and time-dependent manner. A nearly perfect correlation was observed between histatin-induced inhibition of respiration and cell killing with either logarithmic-or stationary-phase cells, but stationary-phase cells were less sensitive. Because nonrespiring yeast cells are insensitive to histatin 5, the potential mechanistic relationship between histatin 5 interference with the respiratory apparatus and cell killing was explored by using an oxygen radical sensitive probe (dihydroethidium). Fluorimetric measurements showed that histatin 5 induced the formation of reactive oxygen species (ROS) in C. albicans cells as well as in isolated mitochondria and that ROS levels were highly correlated with cell death. In the presence of an oxygen scavenger (L-cysteine), cell killing and ROS formation were prevented. In addition, the membrane-permeant superoxide dismutase mimetic 2,2,6,6-tetramethylpiperidine-N-oxyl, abolished histatin-induced ROS formation in isolated mitochondria. In contrast to histatin 5, the conventional inhibitors of the respiratory chain, sodium cyanide or sodium azide, neither induced ROS nor killed yeast cells. These data provide strong evidence for a comprehensive mechanistic model of histatin-5-provoked yeast cell death in which oxygen radical formation is the ultimate and essential step.

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“…Histatin 8 is a known anti-fungal peptide, yet its mode of action remains to be a controversial topic. With a net positive charge and low hydrophobicity it has previously been shown to have membranolytic activity by causing depolarization of membranes (Johnson, Yeh, & Dodds, 2000). To start selective facilitation of microbe membrane disruption, it is said that a strong electrostatic interaction between polar phospholipid head groups of a cell membrane and the cationic face of an AMP must transpire.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Effects of Hydrophobicity and Charge on the Therapeutic Ability of the Antimicrobial Histatin 8 Peptide for Potential Use in Oral Applications

Matheson¹,

Cheeptham²,

Huttunen-Hennelly³

2013

IJB

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Advances in technology allow for the construction of synthetic antibiotics, which includes the development of de novo antimicrobial peptides (AMPs). The contents of AMPs including amino acids, chain length, hydrophobicity, ring structure/rigidity, terminus and charge when modified can alter the antimicrobial properties. A special family of peptides called histatins is naturally excreted by oral glands as an immune response, and previous research shows their potential for treating thrush. Histatin 8 is known to have antimicrobial activity against yeast strains and the goal of this study was to synthesize histatin 8 and two novel derivatives (∆1 and ∆4) that fall at extremes of each other with regard to charge and hydrophobicity in order to investigate the properties that could optimize antimicrobial properties. The derivatives were characterized using various chemical and biological assays to investigate the effects of charge and hydrophobicity on bioactivity. Compared to histatin 8, ∆4's minimum inhibitory concentration (MIC) was decreased more than tenfold against Candida tropicalis indicating increased antimicrobial activity. Re-inoculation confirmed fungicidal properties.

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Effect of donor age on the concentrations of histatins in human parotid and submandibular/sublingual saliva

Cited by 70 publications

References 41 publications

Histatins: antimicrobial peptides with therapeutic potential

Histatins: antimicrobial peptides with therapeutic potential

The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species

Investigating the Effects of Hydrophobicity and Charge on the Therapeutic Ability of the Antimicrobial Histatin 8 Peptide for Potential Use in Oral Applications

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