Strains Of Propionibacterium Acnes Research Articles

Clinical efficacy of 0.5% topical mangosteen extract in nanoparticle loaded gel in treatment of mild-to-moderate acne vulgaris: A 12-week, split-face, double-blinded, randomized, controlled trial.

Acne vulgaris is the most common inflammatory sebaceous gland disorder in young adults. The resistant strains of Propionibacterium acnes (P.acnes) are of increasing concern in the treatment of acne. To evaluate the efficacy of 0.5% topical mangosteen extract in nanoparticle loaded gel (containing alpha-mangostin) compared with 1% clindamycin gel for treatment of mild-to-moderate acne vulgaris. Patients aged 18-40years were enrolled in this double-blinded, split-face, randomized, control study. The 2.5% benzoyl peroxide cream was applied to both sides of the faces once daily for 5 minutes and washed off. Each patient was randomly treated with the mangosteen fruit rind extract on one side and 1% clindamycin on another side of the face twice daily for 12weeks. Treatment efficacies and side effects were evaluated on every follow-up. Twenty-eight patients, 24 female (85.7%), mean ± SD age of 25.14±5.8, with Global Acne Grading system (GAGs) score of 15.43±5.96 were included. Mangosteen fruit rind extract significantly showed significant 66.86% and 67.05% reduction of comedone and inflammatory lesions (P<0.001) after 12-week treatment. The improvement on both treated sides significantly showed since 2weeks after treatment, without statistical difference between two groups. Nonetheless, the mangosteen fruit rind extract revealed significantly better improvement of clinical severity, with no severe side effects. The mangosteen fruit rind extract formation could be a phytopharmaceutical medication for effective treatment of mild and moderate acne vulgaris treatment comparable to 1% clindamycin gel, with no severe side effects.

Hemolytic strains of Propionibacterium acnes do not demonstrate greater pathogenicity in periprosthetic shoulder infections

Hemolysis has been suggested as a feature conferring increased pathogenicity to certain Propionibacterium acnes strains in the setting of shoulder infection. The purpose of this study was to compare the virulence of hemolytic and nonhemolytic P acnes strains in patients undergoing revision shoulder arthroplasty. Thirty-nine patients with at least 1 positive culture growth for P acnes at the time of revision surgery were identified with P acnes isolates available for hemolysis testing. Patients were grouped into those with P acnes isolates positive (n = 20) and negative (n = 19) for hemolysis. The groups were retrospectively compared based on objective perioperative findings around the time of revision surgery and the postoperative clinical course, including the need for revision surgery. All cases were classified into categories of infection (definite infection, probable infection, and probable contaminant) based on objective perioperative criteria. The presence of hemolysis was not significantly associated with an increased likelihood of infection (P = .968). Hemolysis demonstrated a 75% sensitivity and 26% specificity for determining infection (definite infection and probable infection categories). The hemolytic and nonhemolytic groups showed no difference regarding preoperative serum erythrocyte sedimentation rate and/or C-reactive protein level (P = .70), number of positive cultures (P = .395), time to positive culture (P = .302), and presence of positive frozen section findings (P = .501). Postoperatively, clindamycin resistance, shoulder function, and the rate of reoperation were not significantly different between the hemolytic and nonhemolytic groups. The presence of hemolysis was not associated with increased pathogenicity in patients with P acnes-positive cultures following revision shoulder arthroplasty, when assessed by objective perioperative criteria and the postoperative clinical course.

Stemming the tide of antimicrobial resistance: implications for management of acne vulgaris

Acne can cause substantial distress, decreased self-confidence and increased rates of depression and suicidal ideation.1 Topical and oral antibiotics are commonly used to treat acne, due to both antimicrobial and anti-inflammatory mechanisms of action, but they are not always effective and alternatives are available.2 Whereas topical antibiotics predispose to overgrowth of antibiotic resistant bacteria on treated skin sites, oral antibiotics increase the numbers of resistant bacteria not only on the skin but at all body sites with resident commensal microflora. Examples include overgrowth of resistant strains of Propionibacterium acnes 3 and coagulase-negative staphylococci on the skin4 as well as coliforms in the gut. Resistance emerges not only in treated patients but also in close contacts.3,4 A strong case has been made for reducing antibiotic prescribing in primary care but relatively little emphasis has been placed on antibiotic prescribing for acne.5 However, skin conditions account for 8% of primary care antibiotic prescribing and there is rising concern about ‘collateral damage to the steady-state microbiome’ of long-term antibiotic use in young people.3 A recent analysis of the Clinical Practice Research Datalink (CPRD) examined primary care consultations and prescriptions administered for acne.6 This suggested that GPs prescribe oral antibiotics at 31% of first consultations for acne,6 though it is not clear whether this is due to GP prescribing habits or pressure from patients. Over 90% of …

Propionibacterium acnes Strains Differentially Regulate the Fate of Th17 Responses in the Skin

Agak etal. demonstrate that different strains of Propionibacterium acnes, a bacterium colonizing pilosebaceous units in healthy skin and acne, have the ability to induce T helper type 17 cells secreting either IFN-γ or IL-10 and exhibiting either pathogenic or protective properties, respectively. This work contributes to growing evidence indicating that the phenotype of T helper type 17 cells is largely dependent on their microbiological environment.

G2A Attenuates Propionibacterium acnes Induction of Inflammatory Cytokines in Human Monocytes.

BackgroundAcne vulgaris is a disease of the pilosebaceous unit characterized by increased sebum production, hyperkeratinization, and immune responses to Propionibacterium acnes (PA). Here, we explore a possible mechanism by which a lipid receptor, G2A, regulates immune responses to a commensal bacterium.ObjectiveTo elucidate the inflammatory properties of G2A in monocytes in response to PA stimulation. Furthermore, our study sought to investigate pathways by which lipids modulate immune responses in response to PA.MethodsOur studies focused on monocytes collected from human peripheral blood mononuclear cells, the monocytic cell line THP-1, and a lab strain of PA. Our studies involved the use of enzyme-linked immunosorbent, Western blot, reverse transcription polymerase chain reaction, small interfering RNA (siRNA), and microarray analysis of human acne lesions in the measurements of inflammatory markers.ResultsG2A gene expression is higher in acne lesions compared to normal skin and is inducible by the acne therapeutic, 13-cis-retinoic acid. In vitro, PA induces both the Toll-like receptor 2-dependent expression of G2A as well as the production of the G2A ligand, 9-hydroxyoctadecadienoic acid, from human monocytes. G2A gene knockdown through siRNA enhances PA stimulation of interleukin (IL)-6, IL-8, and IL-1β possibly through increased activation of the ERK1/2 MAP kinase and nuclear factor kappa B p65 pathways.ConclusionG2A may play a role in quelling inflammatory cytokine response to PA, revealing G2A as a potential attenuator of inflammatory response in a disease associated with a commensal bacterium.

Draft Genome Sequences of Four Propionibacterium acnes Strains Isolated from Implant-Related Infections.

Propionibacterium acnes was previously described as a potential implant-related pathogen. Here, we report the draft genome sequence of four P. acnes strains, isolated from spine material, hip arthroplasty, and knee arthroplasty infections in France belonging to different sequence types (ST18, ST27, and ST36).

Emendation of Propionibacterium acnes subsp. acnes (Deiko et al. 2015) and proposal of Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov.

Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp. nov., with strains from the type I and II divisions collectively classified as P. acnessubsp. acnes subsp. nov. Under such a taxonomic re-appraisal, we believe that types I and II should also have their own separate rank of subspecies. In support of this, we describe a polyphasic taxonomic study based on the analysis of publicly available multilocus and whole-genome sequence datasets, alongside a systematic review of previously published phylogenetic, genomic, phenotypic and clinical data. Strains of types I and II form highly distinct clades on the basis of multilocus sequence analysis (MLSA) and whole-genome phylogenetic reconstructions. In silico or digital DNA-DNA similarity values also fall within the 70-80 % boundary recommended for bacterial subspecies. Furthermore, we see important differences in genome content, including the presence of an active CRISPR/Cas system in type II strains, but not type I, and evidence for increasing linkage equilibrium within the separate divisions. Key biochemical differences include positive test results for β-haemolytic, neuraminidase and sorbitol fermentation activities with type I strains, but not type II. We now propose that type I strains should be classified as P. acnessubsp. acnes subsp. nov., and type II as P. acnessubsp. defendens subsp. nov. The type strain of P. acnessubsp. acnes subsp. nov. is NCTC 737T (=ATCC 6919T=JCM 6425T=DSM 1897T=CCUG 1794T), while the type strain of P. acnessubsp. defendens subsp. nov. is ATCC 11828 (=JCM 6473=CCUG 6369).

Recent progress in the research about Propionibacterium acnes strain diversity and acne: pathogen or bystander?

Recent progress has steadily reported the existence of the diverse strains of Propionibacterium acnes, and these studies have contributed to the elucidation of their contradictory roles between normal commensals and pathogens. In this review, the authors aimed to provide an update on the recent understanding of research about P. acnes strain diversity and acne, analyzing the potential implications for clinical applications. Before the era of genomic research, P. acnes was known to be distinguished based on serological agglutination tests, cell wall sugar analysis, or fermentation traits. Since the complete genome sequence of P. acnes was first deciphered, genetic studies based on sequence data have expanded with the introduction of more refined and precise DNA-based typing methods, including multilocus sequence typing and metagenomics. These sophisticated techniques have revealed that P. acnes consists of phylogenetically distinct cluster groups with various pathogenic traits, including elicitation of inflammation, protein secretome profile, and unique distribution patterns in various skin loci. In following large-scale studies from patients' acne samples have revealed that specific sequence types are included within the phylogenetic divisions and further suggested that particular P. acnes strains play an etiologic role in acne while others are associated with health, providing a firm platform for evidential-based research into the exact role of this organism in acne. We strongly believe that future research would provide fruitful results in not only clarifying the apparent controversy with respect to roles of P. acnes but also developing therapeutic drugs by pinpointing specific targets of the pathogenic strain only.

Fluctuation of Bacteria on Bleb Surface After Trabeculectomy With Adjunctive Mitomycin C

To determine whether the bacterial and floral patterns on the bleb surface are affected by the season in eyes that had undergone trabeculectomy with adjunctive mitomycin C. Forty-four glaucoma patients who had an avascular or a hypovascular cystic filtering bleb were studied. Swabs of the bleb surface were taken 4 times in 1 year. The samples were cultured, and all organisms isolated were identified and tested for antibiotic sensitivity and resistance. Of the 176 specimens, 48 tested positive in cultures. Out of the 44 glaucoma eyes that had undergone trabeculectomy, 30 (68.2%) eyes were culture positive. A total of 58 strains were isolated. The organisms isolated were 22 strains of Staphylococcus epidermidis, 21 strains of Propionibacterium acnes, 8 strains of Corynebacterium sp., 5 strains of Staphylococcus sp., and 1 strain of both Neisseria sp., and Candida parapsilosis. Fifteen eyes had a positive culture ≥2 times, and in 10 of these eyes, the same strain was isolated. There was no resistance to vancomycin by S. epidermidis, P. acnes, and Corynebacterium sp. All of the isolates of S.epidermidis were sensitive to minocycline and amikacin. The rate of bacterial detection in the spring was 13.6%, summer was 20.5%, autumn was 45.5%, and winter was 29.5%. The increase in the incidence of bacterial presence during autumn was significant (P=0.006; the Fisher exact probability test). It is not rare to detect the bacterial organisms on the bleb surface in glaucomatous eyes that had undergone trabeculectomy. The prevalence varied with the season and was highest in the autumn.

Cross-sectional Pilot Study of Antibiotic Resistance in Propionibacterium Acnes Strains in Indian Acne Patients Using 16S-RNA Polymerase Chain Reaction: A Comparison Among Treatment Modalities Including Antibiotics, Benzoyl Peroxide, and Isotretinoin.

Background:Antibiotic resistance is a worldwide problem in acne patients due to regional prescription practices, patient compliance, and genomic variability in Propionibacterium acnes, though the effect of treatment on the resistance has not been comprehensively analyzed.Aims:Our primary objective was to assess the level of antibiotic resistance in the Indian patients and to assess whether there was a difference in the resistance across common treatment groups.Subjects and Methods:A cross-sectional, institutional based study was undertaken and three groups of patients were analyzed, treatment naïve, those on antibiotics and patients on benzoyl peroxide (BPO) and/isotretinoin. The follicular content was sampled and the culture was verified with 16S rRNA polymerase chain reaction, genomic sequencing, and pulsed-field gel electrophoresis. Minimum inhibitory concentration (MIC) assessment was done for erythromycin (ERY), azithromycin (AZI), clindamycin (CL), tetracycline (TET), doxycycline (DOX), minocycline (MINO), and levofloxacin (LEVO). The four groups of patients were compared for any difference in the resistant strains.Results:Of the 52 P. acnes strains isolated (80 patients), high resistance was observed to AZI (100%), ERY (98%), CL (90.4%), DOX (44.2%), and TETs (30.8%). Low resistance was observed to MINO (1.9%) and LEVO (9.6%). Statistical difference was seen in the resistance between CL and TETs; DOX/LEVO and DOX/MINO (P < 0.001). High MIC90 (≥256 μg/ml) was seen with CL, macrolides, and TETs; moreover, low MIC90 was observed to DOX (16 μg/ml), MINO (8 μg/ml), and LEVO (4 μg/ml). Though the treatment group with isotretinoin/BPO had the least number of resistant strains there was no statistical difference in the antibiotic resistance among the various groups of patients.Conclusions:High resistance was seen among the P. acnes strains to macrolides-lincosamides (AZI and CL) while MINO and LEVO resistance was low.

Antimicrobial efficacy of granulysin-derived synthetic peptides in acne vulgaris.

Antimicrobial peptides are considered as a potential alternative to antibiotic treatment in acne vulgaris because the development of a resistant strain of Propionibacterium acnes is problematic. Granulysin can be regarded as an ideal substance with which to treat acne because it has antimicrobial and anti-inflammatory effects. This study was performed to explore the effectiveness of granulysin-derived peptides (GDPs) in killing P.acnes in vitro under a standard microbiologic assay and to evaluate their potential use in a topical agent for the treatment of acne vulgaris. Twenty different peptides based on the known sequence of a GDP were synthesized and tested in vitro for antimicrobial activity. Thirty patients with facial acne vulgaris were instructed to apply a topical formulation containing synthetic GDP to acne lesions twice per day for 12weeks. A newly synthesized peptide in which aspartic acid was substituted with arginine, and methionine was substituted with cysteine, showed the highest antimicrobial activity against P.acnes. Moreover, it was effective against both Gram-positive and Gram-negative bacteria in vitro. After treatment with the topical formulation containing 50ppm of synthetic peptide for 12weeks, a significant reduction in the number of pustules was observed, regardless of the increase in the number of comedones. In addition, a significant reduction in the clinical grade of acne based on the Korean Acne Grading System (KAGS) was evident. Synthesized GDP shows strong antimicrobial activity against P.acnes in vitro. The clinical improvement observed suggests a topical formulation containing the GDP has therapeutic potential for the improvement of inflammatory-type acne vulgaris by its antimicrobial activity.

Antibiotic Susceptibility Patterns of Propionibacterium Acnes Isolated from Acne Vulgaris in Assiut University Hospitals , Egypt

Background: Antibiotics are frequently used to treat acne patients either as bactericidal or anti-inflammatory agents. However, with the increased use of antibiotics, resistant strains of Propionibacterium acnes began to emerge and have been associated with a poor treatment outcome. Objectives: Detection of staphylococcal and Propionibacterium acnes strains in cases of acne vulgaris in Assiut university hospitals, Egypt and antibiotic susceptibility patterns of Propionibacterium acnes isolates. Methodology: Microbiological samples were obtained from one hundred patients with inflammatory acne lesions. Samples were cultured on blood agar and mannitol salt agar media under aerobic conditions at 37°C for isolation of staphylococcal strains, and on blood agar under anaerobic conditions at 37°C for 3 to 7 days for isolation of Propionibacterium acnes. Bacteria were identified by colonial morphology, standard biochemical tests, and API 20A test for identification of Propionibacterium acnes isolates. Antibiotic sensitivity testing of Propionibacterium acnes strains was done against clindamycin, erythromycin, doxycyclin, trimethoprime/sulfamethxazole, tetracycline and levofloxacin. Results: S taphylocoocal strains were detected in 55% of acne cases, while Propionibacterium acnes were detected in 35% of cases. Most Propionibacterium acnes isolates were sensitive to levofloxacin (80%), followed by doxycycline (51.4%), tetracycline, trimethoprime/ sulfamethaxazole (20.0% for each) while showed highest resistance rates to clindamycin (85.7%) and erythromycin (82.9%). Conclusion: Levofloxacin was the most effective antibiotic for Propionibacterium acnes followed by doxycycline, while Erythromycin and clindamycin were the least effective antibiotics for Propionibacterium acnes.

Use of Yeast Lysate in Women with Recurrent Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) affects a significant number of women, especially in working age. In an estimated 75% of women an episode of acute vulvovaginal candidiasis occurs during lifetime and another 5–10% of women develop recurrent vulvovaginal candidiasis (RVVC). This is mainly characterized by intense burning, itching, pain, abnormal discharge, dyspareunia. Immune response to candidiasis is both cellular (CMI) (natural protection mechanisms) and humoral (antibody production). Understanding the principles of immunity in candidiasis is also important for development of candida vaccines.CANDIVAC contains lyophilized Candida lysate (C. albicans, C. krusei, C. glabrata) together with immunostimulatory bacterial strain of Propionibacterium acnes. The product is taken orally in capsules for 10 days followed by a 20-day pause. It is administered for 3 to 6 months. The product has been tested in a total of 75 women at the age of 18–45 years. In these women at least 4 episodes of vulvovaginal candidiasis have been microscopically or laboratory diagnosed during the last 12 months. Following CANDIVAC administration, statistically significant changes occurred in the evaluation of subjective and some objective criteria. The most important marker of product efficiency is a significant reduction in recurrence compared to the recent state. This criterion has a fundamental importance in patient satisfaction. Before medication the patients suffered from at least 4 attacks, while after medication an attack occurred in only 31% of women and more than 2 attacks in only 3% of treated women.Compromised balance of immune system plays a major role in recurrent vulvovaginal candidiasis. Specific oral product CANDIVAC, prepared from the most common strains of yeast infections, supports immune mechanisms, ensuring resistance of the human organism against yeasts. Its administration significantly prolongs remission, leads to a reduction in application of antimycotics and also changes properties of cellular and humoral immunity in medicated patients.

Bone and joint infections due to anaerobic bacteria: an analysis of 61 cases and review of the literature

The diagnosis of anaerobic bone and joint infections (BJI) were underestimated before the advent of molecular identification and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We report 61 cases of anaerobic infections based on our 4-year experience with the management of BJI. A total of 75% of cases were post-surgical infections, associated with osteosynthesis devices (65%). Early infections occurred in 27% of cases, delayed infections in 17.5% of cases, and late infections in 55% of cases. We recorded 36 species of 93 anaerobic strains using MALDI-TOF MS (91) and molecular methods (2). We identified 20 strains of Propionibacterium acnes, 13 of Finegoldia magna, six of Peptoniphilus asaccharolyticus, and six of P. harei. Polymicrobial infections occurred in 50 cases. Surgical treatment was performed in 93.5% of cases. The antibiotic treatments included amoxicillin (30%), amoxicillin-clavulanic acid (16%), metronidazole (30%), and clindamycin (26%). Hyperbaric oxygen therapy was used in 17 cases (28%). The relapse rate (27%) was associated with lower limbs localization (p = 0.001). P. acnes BJI was associated with shoulder (p = 0.019), vertebra (p = 0.021), and head flap localization (p = 0.011), and none of these cases relapsed (p = 0.007). F. magna BJI was associated with ankle localization (p = 0.014). Anaerobic BJI is typically considered as a post-surgical polymicrobial infection, and the management of this infection combines surgical and medical treatments. MALDI-TOF MS and molecular identification have improved diagnosis. Thus, physicians should be aware of the polymicrobial nature of anaerobic BJI to establish immediate broad-spectrum antibiotic treatment during the post-surgical period until accurate microbiological results have been obtained.

Phage Renaissance: New Hope against Antibiotic Resistance

In the 1920s and 1930s, before widespread use of anti-biotics, physicians successfully treated a variety of infections with bacteriophages, or phages for short. These natural viral predators, which target bacteria but leave mammalian and plant cells unscathed, were sold by pharmaceutical companies including Eli Lilly & Company1 and even made it into the fiction of the time—the protagonist of Sinclair Lewis’ 1925 book Arrowsmith fought bubonic plague with phages.2 Phages on the surface of an Escherichia coli cell inject genetic material into the bacterium. Scientists of the day did not understand exactly how phages killed bacteria, and their crude therapies performed inconsistently. So with the mass production of “magic bullet” antibiotics in the 1940s and 1950s, interest in phages largely waned.1 But 60 years later, antibiotics are losing their luster. Antibiotics have not only been used to treat human infections but also are given to farm animals to speed growth and prevent illness. They end up being flushed down drains and leach into soil and groundwater, where they contribute to environmental hot spots of antibiotic resistance.3 Antibiotic-resistant microbes now pose a growing threat to people of all ages, nationalities, and socioeconomic backgrounds, and previously treatable diseases are becoming untreatable once more.4 Researchers, too, are looking back to the pre-antibiotic era, but with the goal of resurrecting phages as antidotes for antibiotic resistance and solving medical, agricultural, and environmental problems. This time around, they are armed with molecular biology tools to better understand and control phages. They can also draw on the experience of Eastern European investigators, who have continued to study these viruses for decades, publishing their work primarily in Russian, Georgian, and Polish journals.1 In these countries, phages have continued to be given orally as tablets and liquids, topically, rectally, and as injections for 90 years. No reports of serious side effects have been recorded, and fever and other minor side effects came from contaminants like endotoxins in early phage preparations.1

Pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma in vitro.

To understand the pathogen characteristics and its sensitivity against antimicrobial agents in fatal bacterial granuloma after eyelid trauma (FBGT) in vitro, and to provide laboratory evidence for diagnosis. The FBGT pathogens were isolaated and cultured with reformed rabbit-brain anaerobic enriched broth (RRAB), and identified by ATB/API 20A system. The minimum inhibiting concentration (MIC) was determined by anaerobic broth dilution method. A total of 22 strains of pathogen were separated from 21 patients with FBGT and identified as Propionibacterium acnes (PA) by ATB/API 20A system. The MIC of ciprofloxacin for 22 PA strains was 0.0625-0.5mg/L, the MIC of penicillin, ampicillin, ampicillin/sulbactam, cefoperazone, lincomycin, and imipenem/cilastatin were 0.125-0.5mg/L, the MIC of ticarcillin/clavulanic acid was 0.250-1.000 mg/L, and the MIC of metronidazole was 64-256mg/L. The pathogen of FBGT was strictly anaerobic PA, which growed slowly and better in nutritious RRAB broth. All PA were resistant to metronidazole, but susceptive to other routine antimicrobial agents, such as penicillin, ampicillin and lincomycin. [corrected] FBGT should not be treated with metronidazole. Clinicians should choose combined use of drugs or operation to treat FBGT according to patients' individual condition and the results of drug sensitivity test.

Propionibacterium acnes and Sebaceous Lipogenesis: A Love–Hate Relationship?

In this issue, Iinuma et al. show that Propionibacterium acnes (P. acnes)-conditioned medium and formalin-killed P. acnes augment intracellular lipid formation in hamster sebocytes by increasing the de novo synthesis of triacylglycerols. This commentary summarizes the current knowledge of the association of P. acnes with sebaceous lipogenesis, inflammation, and innate immunity, and points out the concurrent evidence that P. acnes-induced lipids may represent a recruitment of allies and/or enemies of the human skin.

Topical clindamycin preparations in the treatment of acne vulgaris

Topical clindamycin has been accepted as being effective, safe and well tolerated in the treatment of acne for decades. Topical clindamycin comes in various vehicles, including gel, lotion, solution and foam. Choosing the proper vehicle is dependent on patient preference, tolerability and application site. Widespread usage of topical antibiotics has led to a greater proportion of resistant strains of Propionibacterium acnes. As a result of the increasing resistance, clindamycin monotherapy is no longer considered a first-line acne treatment. Currently, combination treatment with benzoyl peroxide has helped to prevent antibiotic resistance. In addition, novel combinations, such as clindamycin phosphate 1.2% or tretinoin 0.025% gel, have been proven to be superior to clindamycin monotherapy in reducing acne lesion counts.

Glucocorticoids Enhance Toll-Like Receptor 2 Expression in Human Keratinocytes Stimulated with Propionibacterium acnes or Proinflammatory Cytokines

Toll-like receptors (TLRs) on keratinocytes are important cell surface receptors involved in the innate and acquired immune response to invading microorganisms. In acne vulgaris, TLR2 activation by Propionibacterium acnes (P. acnes) may induce skin inflammation via induction of various proinflammatory molecules that stimulate the invasion of inflammatory cells. Although corticosteroids themselves exert immunosuppressive or anti-inflammatory effects, it is well known clinically that systemic or topical glucocorticoid treatment provokes an acneiform reaction. Nevertheless, the effect of steroids on TLR2 expression in human keratinocytes remains unknown. Here, we found that the addition of glucocorticoids, such as dexamethasone and cortisol, to cultured human keratinocytes increased their TLR2 gene expression. Moreover, these glucocorticoids markedly enhanced TLR2 gene expression, which was further stimulated by P. acnes, tumor necrosis factor-alpha, and IL-1alpha. Gene expression of mitogen-activated protein kinase (MAPK) phosphatase-1 was also increased by the addition of dexamethasone. By using several inhibitors and activators, we found that TLR2 gene induction by glucocorticoids was mediated by the suppression of p38 MAPK activity following induction of MAPK phosphatase-1. These findings strongly suggest that steroid-induced TLR2 together with P. acnes existing as normal resident flora plays an important role in the exacerbation of acne vulgaris as well as in possible induction of corticosteroid-induced acne or in that of rosacea-like dermatitis.

Overview of new therapeutic developments for acne

The pathogenesis of acne is complex and multifactorial, and parallel targeting of various pathogenetic factors with appropriate drugs currently represents the most effective approach for treating this psychologically and physically scarring disease. Current therapeutic developments in acne focus on fixed combinations of substances with complementary effects in order to optimize efficacy and improve patient compliance. Such combinations are topical clindamycin with benzoyl peroxide, an approach that also reduces the emergence of resistant strains of Propionibacterium acnes, as well as the fixed combination of retinoids with antimicrobials, namely a clindamycin phosphate 1.2%/tretinoin 0.025% and an adapalene 0.1%/benzoyl peroxide 2.5% gel combination. Recent studies have demonstrated the clinical efficacy of topical retinoids in maintenance therapy of acne, which supports the currently refined understanding of acne as a chronic disease. New approaches addressed in clinical trials include topical dapsone 5%...