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Antibiotics
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Innate Antimicrobial Defense of Skin and Oral Mucosa
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Innate Antimicrobial Defense of Skin and Oral Mucosa

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 55885

Special Issue Editor

Prof. Dr. Philip W. Wertz

E-Mail Website
Guest Editor
Department of Oral Pathology, Radiology and Medicine, University of Iowa College of Dentistry, Iowa City, IA 52242, USA
Interests: skin barrier; stratum corneum; ceramides; cholesterol; fatty acids; sphingosine; antimicrobial lipids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues:

This special issue intends to review and update our understanding of the antimicrobial defense mechanisms of the skin and oral cavity.  These two environments are quite different in terms of water, pH and nutrient availability, but have some common antimicrobial factors.

The skin surface supports the growth of a limited range of miocroorganisms but provides a hostile environment for others.  The growth of most microorganisms is prevented or limited by the low pH, scarcity of some nutrients such as phosphorus and the presence of antimicrobial peptides, including defensins and cathelicidins, and antimicrobial lipids, including certain fatty acids and long-chain bases.

On the other hand, the oral cavity is a warm, moist, nutrient rich environment which supports the growth of diverse microflora.  Saliva coating the oral soft and hard surfaces determines which microorganisms can adhere to these surfaces.  Some salivary proteins bind to bacteria and prevent their attachment to surfaces.  Other salivary peptides, including defensins, cathelicidins and histatins are antimicrobial.  Antimicrobial salivary proteins include lysozyme, lactoferrin and lactoperoxidase.  There are also antimicrobial fatty acids derived from salivary triglycerides and long-chain bases derived from oral epithelial sphingolipids.

The various antimicrobial factors determine the microbiomes of the skin surface and the oral cavity.  Alterations of these factors can result in colonization by oportunistic pathogens, and this may lead to infection.

Prof. Dr. Philip W. Wertz
Guest Editor

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Keywords

  • skin microbiome
  • oral microbiome
  • fatty acids
  • lauric acid
  • sapienic acid
  • long-chain bases
  • sphingosine
  • dihydrosphingosine
  • 6-hydroxysphingosine
  • phytosphingosine
  • antimicrobial peptides
  • defensens
  • cathelicidins
  • histatins
  • imicrobial proteins
  • lysozyme
  • lactoferrin
  • lactoperoxidase
  • atopic dermatitis

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

7 pages, 197 KiB  
Editorial
Innate Antimicrobial Defense of Skin and Oral Mucosa
by Philip W. Wertz and Sarah de Szalay
Antibiotics 2020, 9(4), 159; https://doi.org/10.3390/antibiotics9040159 - 3 Apr 2020
Cited by 23 | Viewed by 3587
Abstract
This special issue intends to review and update our understanding of the antimicrobial defense mechanisms of the skin and oral cavity. These two environments are quite different in terms of water, pH, and nutrient availability, but have some common antimicrobial factors. The skin [...] Read more.
This special issue intends to review and update our understanding of the antimicrobial defense mechanisms of the skin and oral cavity. These two environments are quite different in terms of water, pH, and nutrient availability, but have some common antimicrobial factors. The skin surface supports the growth of a limited range of microorganisms but provides a hostile environment for others. The growth of most microorganisms is prevented or limited by the low pH, scarcity of some nutrients such as phosphorus and the presence of antimicrobial peptides, including defensins and cathelicidins, and antimicrobial lipids, including certain fatty acids and long-chain bases. On the other hand, the oral cavity is a warm, moist, nutrient rich environment which supports the growth of diverse microflora. Saliva coating the oral soft and hard surfaces determines which microorganisms can adhere to these surfaces. Some salivary proteins bind to bacteria and prevent their attachment to surfaces. Other salivary peptides, including defensins, cathelicidins, and histatins are antimicrobial. Antimicrobial salivary proteins include lysozyme, lactoferrin, and lactoperoxidase. There are also antimicrobial fatty acids derived from salivary triglycerides and long-chain bases derived from oral epithelial sphingolipids. The various antimicrobial factors determine the microbiomes of the skin surface and the oral cavity. Alterations of these factors can result in colonization by opportunistic pathogens, and this may lead to infection. Neutrophils and lymphocytes in the connective tissue of skin and mucosa also contribute to innate immunity. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)

Research

Jump to: Editorial, Review

11 pages, 1456 KiB  
Article
Rosmarinus officinalis L. (Rosemary) Extracts Containing Carnosic Acid and Carnosol are Potent Quorum Sensing Inhibitors of Staphylococcus aureus Virulence
by Seitaro Nakagawa, Greg G. Hillebrand and Gabriel Nunez
Antibiotics 2020, 9(4), 149; https://doi.org/10.3390/antibiotics9040149 - 31 Mar 2020
Cited by 61 | Viewed by 8160
Abstract
Staphylococcus aureus is an opportunistic pathogen and a common cause of skin infection. S. aureus also plays a role in the pathogenesis of the chronic inflammatory skin disease, atopic dermatitis. S. aureus virulence involves activation of the quorum sensing agr operon. In this [...] Read more.
Staphylococcus aureus is an opportunistic pathogen and a common cause of skin infection. S. aureus also plays a role in the pathogenesis of the chronic inflammatory skin disease, atopic dermatitis. S. aureus virulence involves activation of the quorum sensing agr operon. In this paper, we show that the diterpene carnosic acid, present in R. officinalis L. (rosemary) leaves, is a specific inhibitor of S. aureus agr expression as low as 5 μM. Carnosol and rosmarinic acid are two other phytochemicals present in rosemary leaves. Carnosol, but not rosmarinic acid, is also a potent agr expression inhibitor. Natural rosemary extracts containing carnosic acid and carnosol inhibit S. aureus agr expression, both in luciferase reporter strains and in wild type strains isolated from patients with atopic dermatitis. Specific inhibition of S. aureus virulence using topical formulations of rosemary extract may offer a practical approach to preventing and treating flares of atopic dermatitis. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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21 pages, 4535 KiB  
Article
A 28 Day Clinical Assessment of a Lactic Acid-containing Antimicrobial Intimate Gel Wash Formulation on Skin Tolerance and Impact on the Vulvar Microbiome
by Elizabeth Bruning, Ying Chen, Karen A. McCue, Joseph R. Rubino, Jeremy E. Wilkinson and Alan D. G. Brown
Antibiotics 2020, 9(2), 55; https://doi.org/10.3390/antibiotics9020055 - 1 Feb 2020
Cited by 20 | Viewed by 10090
Abstract
While intimate feminine hygiene products are widely used as part of daily cleansing routines, little is known about how these products impact the vulvovaginal area and its microbiome stability. This 4 week clinical study assessed tolerance of a novel gel wash containing lactic [...] Read more.
While intimate feminine hygiene products are widely used as part of daily cleansing routines, little is known about how these products impact the vulvovaginal area and its microbiome stability. This 4 week clinical study assessed tolerance of a novel gel wash containing lactic acid (pH 4.2) for external daily use when used on the external genital area and its effects on skin moisturization, vulvar skin pH, and the vulvar microbiome. After a 7 day pre-study conditioning period, 36 healthy females in three balanced age groups (18–29, 30–44, and 45–55 years) used the gel wash to cleanse their external genital area (mons pubis and vulva) and entire body at least once per day for 28 days. Skin tolerance of the gel wash was assessed by the gynecologist. Effects of the gel wash on vulvar skin microbiota were studied by performing bacterial 16S rRNA and fungal internal transcribed spacer (ITS) microbial richness and diversity analysis. Based on gynecologic assessment after 28 days of use, the gel wash showed acceptable tolerance, with no signs of increased dryness, redness, edema, itching, stinging, or burning. Use of the gel wash was associated with a significant increase in both short-term (single application) and longer-term (daily use for 28 days) skin moisturization. There was no significant change in vulvar skin pH over time with daily product use, and the gel wash did not significantly affect the natural vulvar microbiome species richness or diversity for bacteria or fungi. Results showed that this gel wash is a mild, moisturizing cleanser that maintains the natural pH and microbial diversity of vulvar skin. To our knowledge, this was the first study to assess the effect of an antimicrobial feminine gel wash on the natural pH and vulvar microbiome habitat of the skin using bacterial 16S rRNA and fungal ITS genetic sequencing techniques. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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9 pages, 475 KiB  
Article
HBD3 Induces PD-L1 Expression on Head and Neck Squamous Cell Carcinoma Cell Lines
by Maria Paula Gomez Hernandez, Amber M. Bates, Emily E. Starman, Emily A. Lanzel, Carissa Comnick, Xian Jin Xie and Kim A. Brogden
Antibiotics 2019, 8(4), 161; https://doi.org/10.3390/antibiotics8040161 - 24 Sep 2019
Cited by 8 | Viewed by 3944
Abstract
Human β-defensin 3 (HBD3) is an antimicrobial peptide up-regulated in the oral tissues of individuals with head and neck squamous cell carcinomas (HNSCC) and oral squamous cell carcinomas (SCC) and present in high concentrations in their saliva. In this study, we determined if [...] Read more.
Human β-defensin 3 (HBD3) is an antimicrobial peptide up-regulated in the oral tissues of individuals with head and neck squamous cell carcinomas (HNSCC) and oral squamous cell carcinomas (SCC) and present in high concentrations in their saliva. In this study, we determined if HBD3 contributes to HNSCC pathogenesis by inducing programmed death-ligand 1 (PD-L1) expression on HNSCC cell lines. For this, SCC cell lines SCC4, SCC15, SCC19, SCC25, and SCC99 (5.0 × 104 viable cells) were used. Cells were incubated with IFNγ (0.6 µM) and HBD3 (0.2, 2.0, or 20.0 µM) for 24 h. Cells alone served as controls. Cells were then treated with anti-human APC-CD274 (PD-L1) and Live/Dead Fixable Green Dead Cell Stain. Cells treated with an isotype antibody and cells alone served as controls. All cell suspensions were analyzed in a LSR II Violet Flow Cytometer. Cytometric data was analyzed using FlowJo software. Treatment with IFNγ (0.6 µM) increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. Treatment with HBD3 (20.0 µM) also increased the number of cells expressing PD-L1 (p < 0.05) with respect to controls. However, treatment with IFNγ (0.6 µM) was not significantly different from treatment with HBD3 (20.0 µM) and the numbers of cells expressing PD-L1 were similar (p = 1). Thus, HBD3 increases the number of cells expressing PD-L1. This is a novel concept, but the role HBD3 contributes to HNSCC pathogenesis by inducing PD-L1 expression in tumors will have to be determined. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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8 pages, 6277 KiB  
Article
Female Asthmatic Patients Have Higher Risk to Develop Gemifloxacin-Associated Skin Rash, Highlighting Unique Delayed Onset Characteristics
by Chiou-Mei Wu, Po-Ju Wei, Yu-Ting Shen, Hsu-Liang Chang, Ying-Ming Tsai, Hung-Fang Pan, Yong-Chieh Chang, Yu-Ching Wei and Chih-Jen Yang
Antibiotics 2019, 8(3), 134; https://doi.org/10.3390/antibiotics8030134 - 31 Aug 2019
Cited by 3 | Viewed by 4924
Abstract
Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in [...] Read more.
Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in a university-affiliated hospital in Taiwan. A total of 1358 patients were enrolled, of whom 36 (2.65%) had skin eruptions. The female patients had a significantly higher odds ratio (OR) 2.24 (95% confidence interval (CI) 1.11–4.53, p = 0.021) of having skin eruptions. A history of asthma was also a significant risk factor (OR 2.04, 95% CI = 1.01–4.14, p = 0.043). Female asthmatic patients had the highest risk of skin eruptions (10/129, 7.2%) with an adjusted OR up to 4.45 (95% CI = 1.81–10.93, p < 0.001) compared to male and non-asthmatic patients. Of note, up to 58.3% (21/36) of the patients experienced a skin rash after they had completed and stopped Gemifloxacin. The median onset time was on the second day (ranging one to five days) after completing treatment. We reported that female asthmatic patients have the highest risk of Gemifloxacin-associated skin eruptions in Asia and that they highlighted a unique delayed onset skin rash. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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Review

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17 pages, 668 KiB  
Review
Antimicrobial Activity of Host-Derived Lipids
by Carol L. Fischer
Antibiotics 2020, 9(2), 75; https://doi.org/10.3390/antibiotics9020075 - 11 Feb 2020
Cited by 58 | Viewed by 8358
Abstract
Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial [...] Read more.
Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective. There are indications that the site of action of antimicrobial fatty acids is the bacterial membrane, while the long-chain bases may inhibit cell wall synthesis as well as interacting with bacterial membranes. Research in this area, although still sporadic, has slowly increased in the last few decades; however, we still have much to learn about antimicrobial lipid mechanisms of activity and their potential use in novel drugs or topical treatments. One important potential benefit for the use of innate antimicrobial lipids (AMLs) as antimicrobial agents is the decreased likelihood side effects with treatment. Multiple studies report that endogenous AML treatments do not induce damage to cells or tissues, often decrease inflammation, and are active against biofilms. The present review summarizes the history of antimicrobial lipids from the skin surface, including both fatty acids and sphingoid bases, in multiple human body systems and summarizes their relative activity against various microorganisms. The range of antibacterial activities of lipids present at the skin surface and in saliva is presented. Some observations relevant to mechanisms of actions are discussed, but are largely still unknown. Multiple recent studies examine the therapeutic and prophylactic uses of AMLs. Although these lipids have been repeatedly demonstrated to act as innate effector molecules, they are not yet widely accepted as such. These compiled data further support fatty acid and sphingoid base inclusion as innate effector molecules. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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25 pages, 1227 KiB  
Review
Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails
by R. Smith, J. Russo, J. Fiegel and N. Brogden
Antibiotics 2020, 9(2), 56; https://doi.org/10.3390/antibiotics9020056 - 1 Feb 2020
Cited by 84 | Viewed by 16016
Abstract
The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is [...] Read more.
The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the “microbiota”) that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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