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Cho J.S.,University of California at Los Angeles | Zussman J.,University of California at Los Angeles | Ramos R.I.,University of California at Los Angeles | Garcia N.C.,University of California at Los Angeles | And 7 more authors.
Journal of Investigative Dermatology | Year: 2011

Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1Β contributed to host defense during a wound infection, whereas IL-1Β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies. © 2011 The Society for Investigative Dermatology.


Yu Y.,University of California at Los Angeles | Yu Y.,University of California at Irvine | Champer J.,University of California at Los Angeles | Kim J.,University of California at Los Angeles | Kim J.,Greater Los Angeles Healthcare System Veterans Affairs
EuPA Open Proteomics | Year: 2015

Propionibacterium acnes, plays an important role in acne vulgaris and other diseases. However, understanding of the exact mechanisms of P. acnes pathogenesis is limited. Few studies have investigated its proteome, which is essential for vaccine development. Here, we comprehensively investigate the proteome of P. acnes strain ATCC 6919, including secreted, cell wall, membrane, and cytosolic fractions in three types of growth media. A total of 531 proteins were quantified using an Orbitrap mass spectrometer and bioinformatically categorized for localization and function. Several, including PPA1939, a highly expressed surface and secreted protein, were identified as potential vaccine candidates. © 2015.


Yu Y.,University of California at Los Angeles | Yu Y.,University of California at Irvine | Champer J.,University of California at Los Angeles | Garban H.,University of California at Los Angeles | And 2 more authors.
British Journal of Dermatology | Year: 2015

Propionibacterium acnes is a major commensal of the human skin. However, it is also the pathogen responsible for acne vulgaris and other diseases, such as medical-device infections. Strains of Propionibacterium acnes have long been classified into several different types. Recently, typing systems for this bacterium have taken on an increased importance as different types of P. acnes have been found to be associated with different disease states, including acne. Genetic approaches based on individual or multiple genes have classified P. acnes into types, which have been supported by the sequencing of nearly 100 P. acnes genomes. These types have distinct genetic, transcriptomic and proteomic differences. Additionally, they may have different immune response profiles. Taken together, these factors may account for the different disease associations of P. acnes types. What's already known about this topic? Several methods exist to type different strains of Propionibacterium acnes. Types of P. acnes appear to be associated with different diseases. P. acnes types display several phenotypic differences. What does this study add? Several methods of typing are reviewed and compared. Differences between P. acnes types are assessed and correlated with their disease associations. Future studies regarding P. acnes types are proposed. © 2015 British Association of Dermatologists.


Schmidt N.W.,University of California at Los Angeles | Agak G.W.,University of California at Los Angeles | Deshayes S.,University of California at Los Angeles | Yu Y.,University of California at Los Angeles | And 7 more authors.
Journal of Investigative Dermatology | Year: 2015

Although antibiotics are a common treatment for acne, the difficulties inherent to effective antimicrobial penetration in sebum and selective antimicrobial action in the skin are compounded by increasing resistance of Propionibacterium acnes clinical isolates. To address these problems, we engineered Pentobra, a peptide- aminoglycoside molecule that has multiple mechanisms of antibacterial action and investigated whether it can be a potential candidate for the treatment of acne. Pentobra combines the potent ribosomal activity of aminoglycosides with the bacteria-selective membrane-permeabilizing abilities of antimicrobial peptides. Pentobra demonstrated potent and selective killing of P. acnes but not against human skin cells in vitro. In direct comparison, Pentobra demonstrated bactericidal activity and drastically outperformed free tobramycin (by 5-7 logs) against multiple P. acnes clinical strains. Moreover, electron microscopic studies showed that Pentobra had robust membrane activity, as treatment with Pentobra killed P. acnes cells and caused leakage of intracellular contents. Pentobra may also have potential anti-inflammatory effects as demonstrated by suppression of some P. acnes-induced chemokines. Importantly, the killing activity was maintained in sebaceous environments as Pentobra was bactericidal against clinical isolates in comedones extracts isolated from human donors. Our work demonstrates that equipping aminoglycosides with selective membrane activity is a viable approach for developing antibiotics against P. acnes that are effective in cutaneous environments. © 2015 The Society for Investigative Dermatology.


Zussman J.,University of California at Los Angeles | Ahdout J.,University of California at Los Angeles | Kim J.,University of California at Los Angeles | Kim J.,Greater Los Angeles Healthcare System Veterans Affairs
Journal of the American Academy of Dermatology | Year: 2010

With the rise of the cosmeceutical industry, numerous formulations have surfaced with claims of reducing the clinical manifestations of photoaging. Many of these products capitalize on the positive connection the public makes with vitamins, especially with respect to their antioxidant capabilities. An impressive amount of basic science and clinical research has been conducted in both an attempt to discover novel strategies for preventing detrimental sun damage and to validate the addition of vitamins to skin care products. As dermatologists, it will be essential to provide our patients with substantiated counseling regarding the efficacy of commercial assertions. In this review, we will systematically examine the evidence supporting the use of vitamins in oral and topical formulations and provide a brief summary of the pathogenesis of photoaging. Limitations of this study include that there may be unpublished data or additional studies that may have been overlooked in our comprehensive review of this topic. © 2009 by the American Academy of Dermatology, Inc.


Champer J.,University of California at Los Angeles | Champer J.,Beckman Research Institute | Patel J.,University of California at Los Angeles | Fernando N.,University of California at Los Angeles | And 4 more authors.
AMB Express | Year: 2013

Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens. © 2013 Bel-Rhlid et al.


Agak G.W.,University of California at Los Angeles | Qin M.,University of California at Los Angeles | Nobe J.,University of California at Los Angeles | Kim M.-H.,University of California at Los Angeles | And 7 more authors.
Journal of Investigative Dermatology | Year: 2014

Acne vulgaris is the most common skin disorder affecting millions of people worldwide and inflammation resulting from the immune response targeting Propionibacterium acnes has a significant role in its pathogenesis. In this study, we have demonstrated that P. acnes is a potent inducer of T helper 17 (Th17) and Th1, but not Th2 responses in human peripheral blood mononuclear cells (PBMCs). P. acnes stimulated expression of key Th17-related genes, including IL-17A, RORα, RORc, IL-17RA, and IL-17RC, and triggered IL-17 secretion from CD4 +, but not from CD8 + T cells. Supernatants from P. acnes-stimulated PBMCs were sufficient to promote the differentiation of naive CD4 + CD45RA T cells into Th17 cells. Furthermore, we found that the combination of IL-1β, IL-6, and transforming growth factor-β-neutralizing antibodies completely inhibited P. acnes-induced IL-17 production. Importantly, we showed that IL-17-expressing cells were present in skin biopsies from acne patients but not from normal donors. Finally, vitamin A (all-trans retinoic acid) and vitamin D (1,25-dihydroxyvitamin D3) inhibited P. acnes-induced Th17 differentiation. Together, our data demonstrate that IL-17 is induced by P. acnes and expressed in acne lesions and that both vitamin A and D could be effective tools to modulate Th17-mediated diseases such as acne. © 2014 The Society for Investigative Dermatology.


Taylor E.J.M.,University of California at Los Angeles | Taylor E.J.M.,Greater Los Angeles Healthcare System Veterans Affairs | Yu Y.,University of California at Los Angeles | Yu Y.,University of California at Irvine | And 3 more authors.
Dermatology and Therapy | Year: 2014

Introduction: Resveratrol (3,5,4′-trihydroxystilbene) is an antioxidant that has multiple biologic effects including antimicrobial properties. Acne vulgaris is a disease of the pilosebaceous unit, characterized by an inflammatory host immune response to the bacteria Propionibacterium acnes (P. acnes). This study sought to determine whether resveratrol may be a potential treatment for acne vulgaris.Methods: Colony-forming unit (CFU) assays together with transmission electron microscopy using P. acnes treated with resveratrol or benzoyl peroxide were used to assess antibacterial effects. Blood was drawn from healthy human volunteers, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to assess cytotoxicity in monocytes and keratinocytes.Results: Resveratrol demonstrated sustained antibacterial activity against P. acnes, whereas benzoyl peroxide, a commonly used antibacterial treatment for acne, demonstrated a short-term bactericidal response. A combination of resveratrol and benzoyl peroxide showed high initial antibacterial activity and sustained bacterial growth inhibition. Electron microscopy of P. acnes treated with resveratrol revealed altered bacterial morphology, with loss of membrane definition and loss of well-defined extracellular fimbrial structures. Resveratrol was less cytotoxic than benzoyl peroxide.Conclusion: The sustained antibacterial activity and reduced cytotoxicity versus benzoyl peroxide demonstrated by resveratrol in this study highlight its potential as a novel therapeutic option or adjuvant therapy in the treatment of acne vulgaris. © 2014, The Author(s).

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