Putative pseudolysogeny-dependent phage gene implicated in the superinfection resistance of Cutibacterium acnes.

Objectives: Cutibacterium acnes, formerly Propionibacterium acnes, is a bacterial species characterized by tenacious acne-contributing pathogenic strains. Therefore, bacteriophage therapy has become an attractive treatment route to circumvent issues such as evolved bacterial antibiotic resistance. However, medical and commercial use of phage therapy for C. acnes has been elusive, necessitating ongoing exploration of phage characteristics that confer bactericidal capacity. Methods: A novel phage (Aquarius) was isolated and analyzed. Testing included genomic sequencing and annotation, electron microscopy, patch testing, reinfection assays, and qPCR to confirm pseudolysogeny and putative superinfection exclusion (SIE) protein expression. Results: Given a superinfection-resistant phenotype was observed, reinfection assays and patch tests were performed, which confirmed the re-cultured bacteria were resistant to superinfection. Subsequent qPCR indicated pseudolysogeny was a concomitantly present phenomenon. Phage genomic analysis identified the presence of a conserved gene (gp41) with a product containing Ltp family-like protein signatures which may contribute to phage-mediated bacterial superinfection resistance (SIR) in a pseudolysogeny-dependent manner. qPCR was performed to analyze and roughly quantify gp41 activity, and mRNA expression was high during infection, implicating a role for the protein during the phage life cycle. Conclusions: This study confirms that C. acnes bacteria are capable of harboring phage pseudolysogens and suggests that this phenomenon plays a role in bacterial SIR. This mechanism may be conferred by the expression of phage proteins while the phage persists within the host in the pseudolysogenic state. This parameter must be considered in future endeavors for efficacious application of C. acnes phage-based therapeutics.

The Effect of Aloe vera on Skin and Its Commensals: Contribution of Acemannan in Curing Acne Caused by Propionibacterium acnes.

Aloe vera is one of the most significant therapeutical plant species that belongs to the family Liliaceae. Aloe vera is composed of a high amount of water, with the remainder being dry matter. The dry matter contains a lot of bioactive compounds like carbohydrates, fats, and enzymes, with various therapeutic and antimicrobial properties. It can enhance the proliferation of cells and prevent cell damage by anti-oxidative properties (stimulating the secretion of superoxide dismutase and peroxidase). Human skin is colonized by microbes like fungi (Candida albicans), bacteria (Propionibacterium acnes, Staphylococcus aureus), and mites. These commensals are responsible for skin characteristics such as acidic pH, the pungent smell of sweat, etc. Human fetuses lack skin microbiota, and their skin is colonized after birth. Commensals present on the skin have a crucial role in training the human immune system against other pathogenic microbes. Propionibacterium acnes act as an opportunistic pathogen when the balance between the commensals is disturbed. We also emphasize the recent progress in identifying the aloe metabolite biosynthesis pathways and the associated enzyme machinery. The hyperproliferation of Propionibacterium acnes causes acne, and acemannan plays a significant role in its cure. Hence, we need to consider a new treatment approach based on the root cause of this dysbiosis.

A Literature Review of Cutibacterium Acnes: From Skin Commensal to Pathogen in Shoulder Surgery.

Cutibacterium acnes, previously known as Propionibacterium acnes, is a gram-positive rod in the pilosebaceous glands and commonly implicated in acne vulgaris. Its role in prosthetic joint infections, particularly in shoulder surgeries, has recently gained attention due to its prevalence around the shoulder girdle. This review collates evidence on the pathogenic role of C. acnes in shoulder surgeries, discussing preventive measures, risk factors, clinical presentation, investigation, and treatment strategies. C. acnes infections are complex, often presenting with non-specific symptoms and delayed diagnoses. Risk factors include male sex, presence of hair, shoulder steroid injections, and previous shoulder surgeries. Investigations such as inflammatory markers, synovial fluid analysis, diagnostic arthroscopy, tissue cultures, and advanced molecular techniques like next-generation sequencing and multiplex polymerase chain reaction are explored for their effectiveness in detecting C. acnes. Treatment strategies range from prolonged antibiotics and antibiotic spacers to single-stage and two-stage revision surgeries. Studies indicate that single-stage revision may provide better outcomes compared to two-stage revision. Effective management of C. acnes infections requires careful assessment, relevant investigations, and tailored treatment approaches. This review emphasizes the need for further research to address intraoperative contamination and to develop more efficient diagnostic and treatment methods.

Control of pathogenic bacterial biofilm associated with acne and the anti-inflammatory potential of an essential oil blend.

Acne is one of the most common skin conditions worldwide, with multifactorial origins it affects areas of the skin with hair follicles and sebaceous glands that become clogged. Bacterial incidence aggravates treatment due to resistance to antimicrobial agents and production of virulence factors such as biofilm formation. Based on these information, this study aims to conduct in vitro evaluations of the antibacterial activity of essential oils (EOs), alone and in combination, against Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis in planktonic and biofilm forms. This study also assessed the anti-inflammatory potential (TNF-α) and the effects of EOs on the viability of human keratinocytes (HaCaT), murine fibroblasts (3T3-L1), and bone marrow-derived macrophages (BMDMs). Of all EOs tested, 13 had active action against P. acnes, 9 against S. aureus, and 9 against S. epidermidis at concentrations of 0.125-2.0 mg/mL. Among the most active plant species, a blend of essential oil (BEOs) was selected, with Cymbopogon martini (Roxb.) Will. Watson, Eugenia uniflora L., and Varronia curassavica Jacq., the latter due to its anti-inflammatory action. This BEOs showed higher inhibition rates when compared to chloramphenicol against S. aureus and S. epidermidis, and higher eradication rates when compared to chloramphenicol for the three target species. The BEOs did not affect the cell viability of cell lines evaluated, and the levels of TNF-α decreased. According to these results, the BEOs evaluated showed potential for the development of an alternative natural formulation for the treatment of acne.

Causal effects of skin microbiota on intervertebral disk degeneration, low back pain and sciatica: a two-sample Mendelian randomization study.

OBJECTIVE: The purpose of this study is to use two-sample Mendelian randomization (MR) to investigate the causal relationship between skin microbiota, especially Propionibacterium acnes, and intervertebral disc degeneration (IVDD), low back pain (LBP) and sciatica. METHODS: We conducted a two-sample MR using the aggregated data from the whole genome-wide association studies (GWAS). 150 skin microbiota were derived from the GWAS catalog and IVDD, LBP and sciatica were obtained from the IEU Open GWAS project. Inverse-variance weighted (IVW) was the primary research method, with MR-Egger and Weighted median as supplementary methods. Perform sensitivity analysis and reverse MR analysis on all MR results and use multivariate MR to adjust for confounding factors. RESULTS: MR revealed five skin microbiota associated with IVDD, four associated with LBP, and two with sciatica. Specifically, P.acnes in sebaceous skin environments were associated with reduced risk of IVDD; IVDD was found to increase the abundance of P.acnes in moist skin. Furthermore, ASV010 [Staphylococcus (unc.)] from dry skin was a risk factor for LBP and sciatica; ASV045 [Acinetobacter (unc.)] from dry skin and Genus Rothia from dry skin exhibited potential protective effects against LBP; ASV065 [Finegoldia (unc.)] from dry skin was a protective factor for IVDD and LBP. ASV054 [Enhydrobacter (unc.)] from moist skin, Genus Bacteroides from dry skin and Genus Kocuria from dry skin were identified as being associated with an increased risk of IVDD. Genus Streptococcus from moist skin was considered to be associated with an increased risk of sciatica. CONCLUSIONS: This study identified a potential causal relationship between skin microbiota and IVDD, LBP, and sciatica. No evidence suggests skin-derived P.acnes is a risk factor for IVDD, LBP and sciatica. At the same time, IVDD can potentially cause an increase in P.acnes abundance, which supports the contamination theory.

Investigating Propionibacterium acnes antibiotic susceptibility and response to bacteriophage in vitro and in vivo.

Introduction: A total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model. Methods: Patients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ 2 test. Results: The results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model. Discussion: This study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.

Unveiling the mechanism of essential oil action against skin pathogens: from ancient wisdom to modern science.

Essential oils are among the most well-known phyto-compounds, and since ancient times, they have been utilized in medicine. Over 100 essential oils have been identified and utilized as therapies for various skin infections and related ailments. While numerous commercial medicines are available in different dosage forms to treat skin diseases, the persisting issues include their side effects, toxicity, and low efficacy. As a result, researchers are seeking novel classes of compounds as substitutes for synthetic drugs, aiming for minimal side effects, no toxicity, and high efficacy. Essential oils have shown promising antimicrobial activity against skin-associated pathogens. This review presents essential knowledge and scientific information regarding essential oil's antimicrobial capabilities against microorganisms that cause skin infections. Essential oils mechanisms against different pathogens have also been explored. Many essential oils exhibit promising activity against various microbes, which has been qualitatively assessed using the agar disc diffusion experiment, followed by determining the minimum inhibitory concentration for quantitative evaluation. It has been observed that Staphylococcus aureus and Candida albicans have been extensively researched in the context of skin-related infections and their antimicrobial activity, including established modes of action. In contrast, other skin pathogens such as Staphylococcus epidermidis, Streptococcus pyogens, Propionibacterium acnes, and Malassezia furfur have received less attention or neglected. This review report provides an updated understanding of the mechanisms of action of various essential oils with antimicrobial properties. This review explores the anti-infectious activity and mode of action of essential against distinct skin pathogens. Such knowledge can be valuable in treating skin infections and related ailments.

Therapeutic Effects of Propionibacterium acnes and Lipopolysaccharide from Escherichia coli in Cats with Feline Panleukopenia.

The objective of this study was to investigate the therapeutic effects of inactivated Propionibacterium acnes and lipopolysaccharide derived from Escherichia coli cells in cats affected by feline panleukopenia virus (FPV). A retrospective study of 80 FPV-positive cats was divided into two groups: a treatment group receiving inactivated Propionibacterium acnes and lipopolysaccharide derived from Escherichia coli cells along with supportive treatment and a no-treatment group receiving only supportive treatment. There was no significant difference in the total white blood cell counts between the two groups. However, the total white blood cell counts of both groups were low on day 0 and increased significantly on days 3 and 6 of treatment. Additionally, the white blood cell counts in the treatment group significantly increased during days 3 to 6 compared with those of the no-treatment group (p < 0.01). The mortality rate was not significantly different between the two groups. In a prospective study, the serum and fecal immunoglobulin A (IgA) levels were measured in both groups. There were no significant differences in IgA levels between the two groups in either the serum or feces.

Topical Preparations for Reducing Cutibacterium acnes Infections in Shoulder Surgery: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Cutibacterium acnes (C acnes) is a commensal skin bacterium, primarily found in sebaceous glands and hair follicles, with a high prevalence in the shoulder region. It is the most common pathogenic organism in prosthetic joint infections after shoulder arthroplasty. Because of its low virulence, its diagnosis remains difficult. PURPOSE: To evaluate the relative effects of topical preparations in reducing C acnes in shoulder surgery. STUDY DESIGN: Meta-analysis; Level of evidence, 1. METHODS: We searched the MEDLINE, Embase, PsychINFO, and Cochrane Library databases in March 2022. Randomized controlled trials (RCTs) comparing any form of topical preparation in arthroscopic or open shoulder surgery were included. The primary outcome was a reduction in the number of positive C acnes cultures. Secondary outcomes were adverse events related to the application of topical preparations. We performed a network meta-analysis to facilitate simultaneous comparisons between multiple preparations across studies. We calculated differences between preparations using odds ratios and their 95% CIs. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: The search yielded 17 RCTs (1350 patients), of which 9 were suitable for the network meta-analysis (775 patients). Overall, 2 RCTs were deemed as having a low risk of bias, and 15 raised "some concerns" of bias. Preparations included benzoyl peroxide (BPO), BPO combined with clindamycin, chlorhexidine gluconate, hydrogen peroxide, povidone-iodine, and water with soap. Only BPO resulted in significantly lower odds of a positive C acnes culture compared with placebo or soap and water (odds ratio, 0.12 [95% CI, 0.04-0.36]). There was no statistically significant difference with all other topical preparations. The only adverse events were skin irritation from BPO and chlorhexidine gluconate in a small number of reported cases. CONCLUSION: BPO was the most effective topical agent in reducing the prevalence of C acnes in shoulder surgery. These results were limited by a combination of indirect and direct data. Future studies should focus on establishing the optimal frequency and duration of preoperative BPO to further reduce the burden of C acnes. REGISTRATION: CRD42022310312 (PROSPERO).

Antibacterial activity and mechanism of cell-free supernatants of Lacticaseibacillus paracasei against Propionibacterium acnes.

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.

The effect of different antibiotic combinations in calcium sulfate cement on the growth of Cutibacterium acnes and Staphylococcus periprosthetic shoulder infection isolates.

BACKGROUND: Periprosthetic joint infections (PJI) of the shoulder are a devastating complication of shoulder arthroplasty and are commonly caused by Staphylococcus and Cutibacterium acnes. Absorbable calcium sulfate (CS) beads are sometimes used for delivering antibiotics in PJI. This study evaluates the in vitro effect of different combinations of gentamicin, vancomycin, and ertapenem in beads made from CS cement on the growth of C acnes and coagulase-negative Staphylococcus (CNS) strains. METHODS: Three strains of C acnes and 5 strains of CNS from clinically proven shoulder PJI were cultured and plated with CS beads containing combinations of vancomycin, gentamicin, and ertapenem. Plates with C acnes were incubated anaerobically while plates with Staphylococcus were incubated aerobically at 37 °C. Zones of inhibition were measured at intervals of 3 and 7 days using a modified Kirby Bauer technique, and beads were moved to plates containing freshly streaked bacteria every seventh day. This process was run in triplicate over the course of 56 days. Statistical analysis was conducted using SPSS v. 28 with repeated measures analysis of variance (ANOVA) and pairwise comparisons with Tukey correction. RESULTS: In experiments with C acnes, beads containing ertapenem + vancomycin and vancomycin alone formed the largest zones of inhibition over time (P < .001). In experiments with Staphylococcus, beads containing vancomycin alone formed the largest zones of inhibition over time for all 5 strains (P < .001). Zones of inhibition were 1.4x larger for C acnes than for Staphylococcus with beads containing vancomycin alone. For both C acnes and Staphylococcus, beads containing ertapenem had the strongest initial effect, preventing all bacterial growth in C acnes and almost all growth for Staphylococcus during the first week but dropping substantially by the second week. Beads containing gentamicin alone consistently created smaller zones of inhibition than beads containing vancomycin alone, with vancomycin producing zones 5.3x larger than gentamicin in C acnes and 1.3x larger in Staphylococcus (P < .001). DISCUSSION: These data suggest that for both C acnes and Staphylococcal species, CS beads impregnated with vancomycin were most effective at producing a robust antibiotic effect. Additionally, ertapenem may be a viable supplement in order to create a more potent initial antibiotic effect but is not as effective as vancomycin when used alone. Gentamicin alone was not effective in maintaining consistent and long-term antibiotic effects. These results indicate that amongst the antibiotics currently commercially available to be used with CS, vancomycin is consistently superior to gentamicin in the setting of C. acnes and CNS.

Application of bacteriophage φPaP11-13 attenuates rat Cutibacterium acnes infection lesions by promoting keratinocytes apoptosis via inhibiting PI3K/Akt pathway.

Acne vulgaris caused by antibiotic-resistant Cutibacterium acnes (C. acnes) infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating C. acnes-induced inflammation in rat models. We found that rats infected with C. acnes had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with C. acnes, which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of C. acnes-induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after C. acnes infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by C. acnes and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing C. acnes and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCECutibacterium acnes infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating Cutibacterium acnes. Bacteriophages are currently proven effective in MDR (multiple drug-resistant) Cutibacterium acnes, but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing Cutibacterium acnes. However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.

The Microbiome and Acne: Perspectives for Treatment.

The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a key factor in acne development, regulating inflammatory and immune pathways. Dysbiosis has been described as the imbalance in skin microbiome homeostasis and may play a role in acne pathogenesis. Microbial interference has been shown to be a contributor to healthy skin homeostasis and staphylococcal strains may exclude acne-associated C. acnes phylotypes. In this review we present an update on the skin microbiome in acne and discuss how current acne treatments such as benzoyl peroxide, orally administered isotretinoin, and antibiotics may affect the skin microbiome homeostasis. We highlight the collateral damage of acne antibiotics on the skin microbiome, including the risk of antimicrobial resistance and the dysregulation of the microbiome equilibrium that may occur even with short-term antibiotic courses. Consequently, the interest is shifting towards new non-antibiotic pharmacological acne treatments. Orally administered spironolactone is an emerging off-label treatment for adult female patients and topical peroxisome proliferator-activated receptor gamma (PPARγ) modulation is being studied for patients with acne. The potential application of topical or oral probiotics, bacteriotherapy, and phage therapy for acne are further promising areas of future research.

Detection of Cutibacterium (Propionibacterium) acnes in orthopaedic surgery: serious problem or contamination?

PURPOSE: Bone and joint infections are an important and increasing problem. Whether intraoperatively detected bacteria should be considered relevant or not is often difficult to assess. This retrospective cohort study analyzes the relevance of C. acnes cultured from deep intraoperative specimens. METHODS: All deep tissue samples collected intraoperatively between 2015 and 2020 from a quartiary care provider were evaluated for detection of C. acnes and its therapeutical consequences. Infection rates were determined according to a standardized definition and protocol and analyzed in dependence of patient's demographic data (age and gender), operative parameters (type of surgery, body region/location of surgery, and impression of the surgeon), and initiated therapy. RESULTS: In 270 cases of more than 8500 samples, C. acnes was detected. In 30%, the detection was considered an infection. The number of samples taken and tested positive for C. acnes correlated significantly with its classification as a cause of infection. If more than one sample of the patient was positive, the detection was significantly more likely to be treated as infection (p < 0.001). In 76% of cases, a consultation to the infectious diseases (ID) department took place regarding the classification of the pathogen detection and the therapy to be carried out. Almost all of the tested isolates demonstrated the wild-type susceptibility for penicillin and clindamycin. CONCLUSION: Intraoperative detection of skin-colonizing bacteria such as C. acnes is not always synonymous with infection. In particular, if other examination results contradict an infection (pathological sample without evidence of an infectious event, detection of malignant cells, etc.), the situation must be considered in a very differentiated manner. Interdisciplinary boards, for example, are suitable for this purpose. Care should be taken to obtain a sufficiently large number of tissue samples for microbiological examination to be able to better classify the result.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge

ABSTRACT In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge.

In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Correlation between Antimicrobial Resistant Propionibacterium acnes and Severity of Acne Vulgaris: Findings from a Tertiary Hospital.

The study of antimicrobial-resistant Propionibacterium acnes was not conducted regularly, especially in Indonesia. Conversely, regular monitoring of antibiotic efficacy through in vitro testing to assess the evolution of current resistance patterns is obligated; thus, filling the gap caused by a lack of appropriate antibiotic surveillance is required. Analyse the correlation between resistance patterns of P. acnes to doxycycline, clindamycin, erythromycin and azithromycin with the severity of acne vulgaris. This is an analytic observational laboratory study with a cross-sectional design of mild to severe acne vulgaris (AV) patients. Specimens were obtained from comedones of 71 patients, which were cultured and identified using biochemical examination. Antimicrobial resistance (doxycycline, clindamycin, erythromycin and azithromycin) to P. acnes was tested by disc diffusion method. Among 71 samples collected, 40 (56.3%) P. acnes isolates were cultured and identified. The incidence of P. acnes resistance to more than one antimicrobial was 45%. Antimicrobial resistances were clindamycin 42.5%, erythromycin 40%, azithromycin 23.5% and doxycycline 12.5%, respectively. According to the contingency coefficient test, there was moderate correlation between the resistance pattern of P. acnes to clindamycin (r = 0.485, P = <0.001) and doxycycline (r = 0.433, P = 0.002) and AV severity. There was weak correlation between the resistance pattern of P. acnes to erythromycin (r = 0.333; P = 0.025) and azithromycin (r = 0.321; P = 0.032) and AV severity. In conclusion, there is a correlation between the pattern of P. acnes resistance to doxycycline, clindamycin, erythromycin, azithromycin and severity of AV.

Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

Active Ingredients of Schisandra chinensis Fruit Oil and their Effect on Propionibacterium acnes-Induced Inflammation in HaCaT Cells.

BACKGROUND: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1ß, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. METHODS: In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO's anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry. RESULTS: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. CONCLUSIONS: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.

Integration of CoAl-Layered Double Hydroxides on Commensal Bacteria to Enable Targeted Tumor Inhibition and Immunotherapy.

Combining targeted therapy and immunotherapy brings hope for a complete cancer cure. Due to their selective colonization and immune activation capacity, some bacteria have the potential to realize targeted immunotherapy. Herein, a biohybrid system was designed and synthesized by cladding NO3--intercalated cobalt aluminum layered double hydroxides (LDH) on anaerobic Propionibacterium acnes (PA) (PA@LDH). In this system, the covering of LDH reduces the pathogenicity of PA to normal tissues and alters its surface charge for prolonged in vivo circulation. Once the tumor site is reached, the acid-responsive degradation of LDH enables PA exposure. PA can colonize and convert nitrate ions to nitric oxide (NO) through denitrification. Then, NO reacts with intracellular O2·- to produce toxic reactive nitrogen species ONOO- and induce tumor cell apoptosis. In addition, cobalt ions released from LDH can inhibit the activity of superoxide dismutase (SOD), thus increasing the level of O2·- and further enhancing the antitumor effect. Moreover, PA exposure activates M2-to-M1 macrophage polarization and a range of immune responses, thereby achieving a sustained antitumor activity. In vitro and in vivo results reveal that the biohybrid system eliminates solid tumors and inhibits tumor metastasis effectively. Overall, the biohybrid strategy provides a new avenue for realizing simultaneous immunotherapy and targeted therapy.