Presence of wax esters and squalene in human saliva

Brasser, Andrew J.; Barwacz, Christopher A.; Dawson, Deborah V.; Brogden, Kim A.; Drake, David R.; Wertz, Philip W.

doi:10.1016/j.archoralbio.2010.12.002

Cited by 29 publications

(41 citation statements)

References 22 publications

(19 reference statements)

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“…Saliva contains neutral lipids; cholesterol; mono-, di-, and tri-glycerides; free fatty acids; wax esters; cholesterol esters; squalene; and long-chain sphingoid bases (Brasser et al, 2010; Brasser et al, 2011a; Brasser et al, 2011b; Defago et al, 2011; Kensche et al, 2013; Larsson et al, 1996; Palmerini et al, 2011). Many of these lipids have innate immune functions: they are antimicrobial, influence the interaction of oral microorganisms with the salivary pellicle, impede microbial adherence to oral surfaces, and create a hydrophobic layer protecting teeth from demineralization (Bibel et al, 1992; Kensche et al, 2013).…”

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confidence: 99%

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

et al. 2015

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Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 µM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propridium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2 to 10.0 µM long-chain bases and GML were not cytotoxic; 40.0 to 80.0 µM long-chain bases, but not GML, were cytotoxic; and 80.0 µM long-chain bases induced cellular damage and death in less than 20 minutes. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.

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Section: Introductionmentioning

confidence: 99%

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

et al. 2015

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“…More recently, the same lipids have been shown to be present in the oral cavity, in saliva and at mucosal surfaces (5,6). The fatty acids are derived from sebaceous triglycerides, while sphingoid bases are derived from epithelial sphingolipids through the action of hydrolytic enzymes.…”

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“…Epithelial layers contain ceramides, free fatty acids, and cholesterol; sebaceous lipids at the skin surface include a complex mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters; and saliva contains the same sebaceous lipids (6,14,19). These sebaceous secretions contribute to (i) the transport of fatsoluble antioxidants to the skin and mucosal surfaces, (ii) the proand anti-inflammatory properties of the skin and mucosal surfaces, and (iii) the innate antimicrobial activity of the skin and mucosal surfaces (20,26,27).…”

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Antibacterial Activity of Sphingoid Bases and Fatty Acids against Gram-Positive and Gram-Negative Bacteria

Fischer

Drake

Dawson

et al. 2012

Antimicrob Agents Chemother

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There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity-the sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine and the fatty acids sapienic acid and lauric acid-against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. D-Sphingosine (MBC range, 0.3 to 19.6 g/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 g/ml), and phytosphingosine (MBC range, 3.3 to 62.5 g/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 g/ml). Sapienic acid (MBC range, 31.3 to 375.0 g/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 g/ml). Lauric acid (MBC range, 6.8 to 375.0 g/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 g/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fatty acids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection.C ommon sphingolipids and fatty acids are involved in the physical barrier, permeability barrier, and immunologic barrier functions of the skin and oral mucosa (8,14). Epithelial layers contain ceramides, free fatty acids, and cholesterol; sebaceous lipids at the skin surface include a complex mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters; and saliva contains the same sebaceous lipids (6,14,19). These sebaceous secretions contribute to (i) the transport of fatsoluble antioxidants to the skin and mucosal surfaces, (ii) the proand anti-inflammatory properties of the skin and mucosal surfaces, and (iii) the innate antimicrobial activity of the skin and mucosal surfaces (20,26,27).Although the composition, biosynthesis, secretion, and function of cutaneous lipids are well characterized from extensive and elegant work done in the 1970s, little is known about their role in controlling microbial infection and colonization. Certain fatty acids and sphingoid bases found at the skin and mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role than previously thought in innate immune defense against epidermal and mucosal bacterial infections (10). They include free sphingosines, dihydrosphingosines, lauric acid, and sapienic aci...

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“…Among these innate immune molecules contributing to the control of oral bacteria are several lipids (10,11). Saliva and mucosal epithelial surfaces contain multiple lipid families, including fatty acids, triglycerides, ceramides, wax esters, cholesterol esters, phospholipids, sterols, sterol esters, and squalene (12)(13)(14)(15). Fatty acids of sebaceous origin are particularly potent antimicrobial agents against a wide range of both Gram-negative and Gram-positive bacteria, exhibiting differential and dose-dependent antimicrobial activity that is both bacterium and lipid specific (16)(17)(18)(19)(20)(21).…”

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Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

et al. 2016

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Lipids endogenous to skin and mucosal surfaces exhibit potent antimicrobial activity against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Our previous work demonstrated the antimicrobial activity of the fatty acid sapienic acid (C 16:1⌬6 ) against P. gingivalis and found that sapienic acid treatment alters both protein and lipid composition from those in controls. In this study, we further examined whole-cell protein differences between sapienic acidtreated bacteria and untreated controls, and we utilized open-source functional association and annotation programs to explore potential mechanisms for the antimicrobial activity of sapienic acid. Our analyses indicated that sapienic acid treatment induces a unique stress response in P. gingivalis resulting in differential expression of proteins involved in a variety of metabolic pathways. This network of differentially regulated proteins was enriched in protein-protein interactions (P ‫؍‬ 2.98 ؋ 10 ؊8 ), including six KEGG pathways (P value ranges, 2.30 ؋ 10 ؊5 to 0.05) and four Gene Ontology (GO) molecular functions (P value ranges, 0.02 to 0.04), with multiple suggestive enriched relationships in KEGG pathways and GO molecular functions. Upregulated metabolic pathways suggest increases in energy production, lipid metabolism, iron acquisition and processing, and respiration. Combined with a suggested preferential metabolism of serine, which is necessary for fatty acid biosynthesis, these data support our previous findings that the site of sapienic acid antimicrobial activity is likely at the bacterial membrane. IMPORTANCE P. gingivalis is an important opportunistic pathogen implicated in periodontitis.Affecting nearly 50% of the population, periodontitis is treatable, but the resulting damage is irreversible and eventually progresses to tooth loss. There is a great need for natural products that can be used to treat and/or prevent the overgrowth of periodontal pathogens and increase oral health. Sapienic acid is endogenous to the oral cavity and is a potent antimicrobial agent, suggesting a potential therapeutic or prophylactic use for this fatty acid. This study examines the effects of sapienic acid treatment on P. gingivalis and highlights the membrane as the likely site of antimicrobial activity. Inflammation in the oral cavity ranges from mild and reversible inflammation of the gingiva (gingivitis) to a more chronic inflammation and destruction of tooth-supporting structures (periodontitis). Gingivitis occurs in 50 to 90% of adults worldwide, depending on the widely differing definitions of gingivitis (1). Periodontitis occurs in just over 47% of the U.S. population, with prevalences of 8.7, 30.0, and 8.5% for mild, moderate, and severe periodontitis depending on multiple factors, including oral hygiene, socioeconomic status, educational status, age, and other environmental, genetic, and metabolic risk factors (2). These numbers differ in different populations, and older individuals are at a particular...

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Presence of wax esters and squalene in human saliva

Cited by 29 publications

References 22 publications

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

Antibacterial Activity of Sphingoid Bases and Fatty Acids against Gram-Positive and Gram-Negative Bacteria

Protein Analysis of Sapienic Acid-Treated Porphyromonas gingivalis Suggests Differential Regulation of Multiple Metabolic Pathways

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