Host–Biofilm Interactions at Mucosal Surfaces and Implications in Human Health
Chaminda Jayampath Seneviratne in Microbial Biofilms, 2017
Histatins belong to a family of small histidine-rich peptides. They are produced by the salivary glands (submandibular, sublingual, parotid glands) and von Ebner’s gland at the back of the tongue. Histatins exert antifungal and antibacterial activity, thereby playing a central role in maintaining good oral health. In humans, histatins 1, 3 and 5 have been described. Histatins 1 and 3 are encoded by two closely related genes. Among all the histatins, histatin 5 is a product processed from histatin 3 and demonstrates the most potent antifungal activity against pathogenic fungi including Aspergillus fumigatus, Cryptococcus neoformans and C. albicans. The exact mode of action of histatins in killing fungi is not clear. Earlier studies showed that histatin 5 interferes with Candida respiration by targeting the mitochondria [145,146]. Later studies have shown histatin 5 disrupts the Candida cell membrane by binding to the potassium ion transporter Trk1. This results in the loss of intracellular potassium and ATP leading to activation of cell death pathway [147].
Interactions between Oral Bacteria and Antibacterial Polymer-Based Restorative Materials
Mary Anne S. Melo in Designing Bioactive Polymeric Materials for Restorative Dentistry, 2020
Antimicrobial peptides (AMPs) derived from histatin 5, lactoferrin, and parotid secretory proteins (P113, hLf-11, and GL13K, respectively)[163–167] have also been recently incorporated and immobilized into experimental polymer-based materials. As previously reviewed, the objective of using these orally expressed peptides (from both organic and synthetic origins) is to develop dental biomaterials with strong antimicrobial functionalities, minimum cytotoxicity to mammalian cells, and low ability to induce resistant bacterial strains.[168] In general terms, these positively charged molecules express their antibacterial behavior through a structure-specific mechanism that preferentially targets the outer membrane and cell wall (both negatively charged) in Gram-positive and Gram-negative bacteria, and results in membrane perforation with consequent disruption of cellular integrity and cell death.[169] Balhara et al.,[166] while investigating the membrane selectivity to GL13K AMP, have demonstrated that these molecules are capable of disrupting the lipid bilayers through a partial micellization and transient pore mechanism. Their results have indicated that GL13K is effective against biofilm-forming bacteria (both Gram-positive and Gram-negative).
Secreted effectors of the innate mucosal barrier
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
In addition to binding microbes, some mucin oligosaccharides have direct antimicrobial activity or can bind to other antimicrobial molecules. The gastric mucin oligosaccharide, α1-4-linked N-acetylglucosamine, inhibits synthesis of H. pylori cell-wall components and may limit H. pylori expansion in gastric mucus. The MUC7 mucin, a major component of saliva, has an N-terminal histatin domain with direct candidacidal activity and thus acts to limit growth of yeast in saliva. Mucins also directly bind antimicrobial molecules. For example, MUC7 binds statherin and histatin-1, and the other major mucin in saliva, MUC5B, binds histatin-1, -3, and -5 and statherin, retaining the antimicrobial molecules in the mucus.
In Vivo Efficacy of Histatin-1 in a Rabbit Animal Model
Published in Current Eye Research, 2018
Marko Oydanich, Seth P. Epstein, Neha Gadaria-Rathod, John J. Guers, Karen B. Fernandez, Penny A. Asbell
While many of these experimental agents were successful in healing wounds on the corneal epithelium, they do so by stimulating cellular proliferation as well as cellular migration. Therefore, the issue of potential neovascularization and inflammation secondary to topical application of the agent, has to be addressed.31 Our study showed no adverse complications while using histatin-1 on rabbits. Additionally, it should be noted that these agents are chemically synthesized and not produced naturally in the body. Histatin-1, on the other hand, is found in saliva and the lacrimal epithelium in both accessory and main lacrimal glands, as well as the conjunctival epithelium.14,32 Therefore the possibility for immune mobilization, adverse reactions, and toxicity are significantly reduced.
Relationship between human immunodeficiency virus (HIV-1) infection and chronic periodontitis
Published in Expert Review of Clinical Immunology, 2018
Tábata Larissa S. Pólvora, Átila Vinícius V. Nobre, Camila Tirapelli, Mário Taba, Leandro Dorigan de Macedo, Rodrigo Carvalho Santana, Bruno Pozzetto, Alan Grupioni Lourenço, Ana Carolina F. Motta
Histatin, a salivary antimicrobial peptide with powerful antifungal action, mainly against C. albicans, and effective control on oral homeostasis, is another antimicrobial peptide of great importance in the pathogenesis of oral diseases [97,98]. In vitro studies have demonstrated that histatin has the ability to eliminate C. albicans in a dose-dependent manner [99,100]. Histatin binds to fungal membrane receptors and is translocated into the cell where it targets the energized mitochondria, causing the release of ATP, calcium and magnesium, and leading to cell death (Figure 4) [77]. The first study that described the ATP efflux of C. albicans in response to histatin-5 showed that extracellular ATP, released from C. albicans by histatin-5, can activate membrane ATP receptors to cause cell death [98,101]. Although the antimicrobial activity of histatin-5 has been extensively studied, there are still few studies evaluating salivary histatin levels in HIV-1-infected subjects with oral disease [102,103], which reported lower salivary levels of histatin-5 in association with higher Candida spp colonization in HIV-1-infected patients than in noninfected patients. These results plead for a higher risk of developing candidiasis in the former population.
Enterotoxigenic Escherichia coli: intestinal pathogenesis mechanisms and colonization resistance by gut microbiota
Published in Gut Microbes, 2022
Yucheng Zhang, Peng Tan, Ying Zhao, Xi Ma
Antimicrobial peptides (AMPs), which are synthesized by diverse organisms or synthetically, are used to fight bacterial infection due to their broad-spectrum antimicrobial activity.182,183 Saliva antimicrobial peptide histatin-5 was shown to inhibit ETEC adhesion and colonization, demonstrating that saliva components combat pathogens introduced through the mouth, which is a component of the innate immune system.184 In an ETEC challenged mouse model, the Lasso peptide Microcin J25 improved epithelial barrier function by increasing tight junctions expression in the small intestine, and alleviated gut inflammatory responses.185 Application of AMPs has the potential to be a beneficial and protective method for ETEC infection. Furthermore, AMPs benefited the intestinal barrier function, inflammatory response, and gut microbiota when ETEC was challenge.186,187
Related Knowledge Centers
- Histidine
- Antimicrobial Peptides
- Saliva
- Innate Immune System
- Homeostasis
- Serous Fluid
- Von Ebner'S Gland
- Acinus
- Proteolysis
- Histatin 3