Study on Oleum cinnamomi Inhibiting Cutibacterium acnes and Its Covalent Inhibition Mechanism.

Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.

Antimicrobial Activity of Positively Charged Oligopeptides with Theoretical High α-Helix Content against Cutibacterium acnes.

Cutibacterium acnes is abundant and commonly exists as a superficial bacteria on human skin. Recently, the resistance of C. acnes to antimicrobial agents has become a serious concern, necessitating the development of alternative pharmaceutical products with antimicrobial activity against C. acnes. To address this need, we evaluated the antimicrobial activity of CKR-13-a mutant oligopeptide of FK-13 with increased net charge and theoretical α-helical content-against C. acnes in modified Gifu Anaerobic Medium broth by determining the minimum inhibitory concentration (MIC). CKR-13 exerted greater antimicrobial activity against C. acnes than FK-13 in the broth at pH 7.0. The antimicrobial activity of CKR-13 with RXM against C. albicans was pH-dependent. The ionization of CKR-13 and pH-dependent growth delay of C. albicans was suggested to be associated with the increase in CKR-13 antimicrobial activity.

Increased biofilm formation in dual-strain compared to single-strain communities of Cutibacterium acnes.

Cutibacterium acnes is a known opportunistic pathogen in orthopedic implant-associated infections (OIAIs). The species of C. acnes comprises distinct phylotypes. Previous studies suggested that C. acnes can cause single- as well as multi-typic infections, i.e. infections caused by multiple strains of different phylotypes. However, it is not known if different C. acnes phylotypes are organized in a complex biofilm community, which could constitute a multicellular strategy to increase biofilm strength and persistency. Here, the interactions of two C. acnes strains belonging to phylotypes IB and II were determined in co-culture experiments. No adverse interactions between the strains were observed in liquid culture or on agar plates; instead, biofilm formation in both microtiter plates and on titanium discs was significantly increased when combining both strains. Fluorescence in situ hybridization showed that both strains co-occurred throughout the biofilm. Transcriptome analyses revealed strain-specific alterations of gene expression in biofilm-embedded cells compared to planktonic growth, in particular affecting genes involved in carbon and amino acid metabolism. Overall, our results provide first insights into the nature of dual-type biofilms of C. acnes, suggesting that strains belonging to different phylotypes can form biofilms together with additive effects. The findings might influence the perception of C. acnes OIAIs in terms of diagnosis and treatment.

Antibacterial toner exhibits bactericidal effect against Cutibacterium acnes via keratin and sebum plug penetration.

Cutibacterium acnes is an opportunistic pathogen recognized as a contributing factor to acne vulgaris. The accumulation of keratin and sebum plugs in hair follicles facilitates C. acnes proliferation, leading to inflammatory acne. Although numerous antimicrobial cosmetic products for acne-prone skin are available, their efficacy is commonly evaluated against planktonic cells of C. acnes. Limited research has assessed the antimicrobial effects on microorganisms within keratin and sebum plugs. This study investigates whether an antibacterial toner can penetrate keratin and sebum plugs, exhibiting bactericidal effects against C. acnes. Scanning electron microscopy and next-generation sequencing analysis of the keratin and sebum plug suggest that C. acnes proliferate within the plug, predominantly in a biofilm-like morphology. To clarify the potential bactericidal effect of the antibacterial toner against C. acnes inside keratin and sebum plugs, we immersed the plugs in the toner, stained them with LIVE/DEAD BacLight Bacterial Viability Kit to visualize microorganism viability, and observed them using confocal laser scanning microscopy. Results indicate that most microorganisms in the plugs were killed by the antibacterial toner. To quantitatively evaluate the bactericidal efficacy of the toner against C. acnes within keratin and sebum, we immersed an artificial plug with inoculated C. acnes type strain and an isolate collected from acne-prone skin into the toner and obtained viable cell counts. The number of the type strain and the isolate inside the artificial plug decreased by over 2.2 log and 1.2 log, respectively, showing that the antibacterial toner exhibits bactericidal effects against C. acnes via keratin and sebum plug penetration.

Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin.

Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis. Integrated genome, transcriptome, and metabolome analysis at the strain level unveils the functional characteristics of C. acnes. Consistent with the transcriptome signature, C. acnes in a sebum-rich environment induces toxic and pro-inflammatory effects on keratinocytes. L-carnosine, an anti-oxidative stress metabolite, is up-regulated in the C. acnes metabolome from atopic dermatitis and attenuates skin inflammation. Collectively, our study reveals the joint impact of genes and the microenvironment on C. acnes function.

Anti-CAMP1 IgG promotes macrophage phagocytosis of Cutibacterium acnes type II.

Among 5 types of the Christie-Atkins-Munch-Petersen factor (CAMP) of Cutibacterium acnes, CAMP1 is highly expressed in phylotype II as well as IB, and thought to be a virulence factor of opportunistic but fatal blood, soft tissue, and implant-related infections. The target of a human single-chain variable antibody fragment (scFv), recently isolated from a phage display library, has been identified as CAMP1 of phylotype II, using immunoprecipitation followed by mass spectrometry, phage display peptide biopanning, 3D-modelling, and ELISA. The IgG1 format of the antibody could enhance phagocytosis of C. acnes DMST 14916 by THP-1 human monocytes. Our results suggest that the antibody-dependent phagocytosis process is mediated by the caveolae membrane system and involves the induction of IL-1ß. This is the first report on the study of a human antibody against CAMP1 of C. acnes phylotype II, of which a potential use as therapeutic antibody against virulence C. acnes infection is postulated.

Comprehensive lipidomic analysis of the genus Cutibacterium.

Cutibacterium are part of the human skin microbiota and are opportunistic microorganisms that become pathogenic in immunodeficient states. These lipophilic bacteria willingly inhabit areas of the skin where sebaceous glands are abundant; hence, there is a need to thoroughly understand their metabolism. Lipids are no longer considered only structural elements but also serve as signaling molecules and may have antigenic properties. Lipidomics remains a major research challenge, mainly due to the diverse physicochemical properties of lipids. Therefore, this study aimed to perform a large comparative lipidomic analysis of eight representatives of the Cutibacterium genus, including four phylotypes of C. acnes and two strains of C. granulosum, C. avidum, and C. namnetense. Lipidomic analysis was performed by liquid chromatography‒mass spectrometry (LC-MS) in both positive and negative ion modes, allowing the detection of the widest range of metabolites. Fatty acid analysis by gas chromatography‒mass spectrometry (GC-MS) corroborated the lipidomic data. As a result, 128 lipids were identified, among which it was possible to select marker compounds, some of which were characteristic even of individual C. acnes phylotypes. These include phosphatidylcholine PC 30:0, sphingomyelins (SM 33:1, SM 35:1), and phosphatidylglycerol with an alkyl ether substituent PG O-32:0. Moreover, cardiolipins and fatty acid amides were identified in Cutibacterium spp. for the first time. This comparative characterization of the cutibacterial lipidome with the search for specific molecular markers reveals its diagnostic potential for clinical microbiology. IMPORTANCE: Cutibacterium (previously Propionibacterium) represents an important part of the human skin microbiota, and its role in clinical microbiology is growing due to opportunistic infections. Lipidomics, apart from protein profiling, has the potential to prove to be a useful tool for defining the cellular fingerprint, allowing for precise differentiation of microorganisms. In this work, we presented a comparative analysis of lipids found in eight strains of the genus Cutibacterium, including a few C. acnes phylotypes. Our results are one of the first large-scale comprehensive studies regarding the bacterial lipidome, which also enabled the selection of C. acnes phylotype-specific lipid markers. The increased role of lipids not only as structural components but also as diagnostic markers or potential antigens has led to new lipid markers that can be used as diagnostic tools for clinical microbiology. We believe that the findings in our paper will appeal to a wide range of researchers.

Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer.

BACKGROUND: Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer. METHODS: To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of nonhuman sequences from RNA-seq data. RESULTS: We identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant changes in homologous recombination (HR) and the Fanconi anemia pathway. Notably, electron microscopy demonstrated that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assays demonstrated impaired HR repair. In particular, BRCA2 was significantly downregulated in C. acnes-infected cells. CONCLUSIONS: These findings suggest that C. acnes infection in the prostate could lead to HR deficiency (BRCAness) which promotes DNA double-strand breaks, thereby increasing the risk of cancer development.

Acceptor-Reactivity-Controlled Stereoconvergent Synthesis and Immunological Activity of a Unique Pentasaccharide from the Cell Wall Polysaccharide of Cutibacterium acnes C7.

Bacterial cell-surface polysaccharides are involved in various biological processes and have attracted widespread attention as potential targets for developing carbohydrate-based drugs. However, the accessibility to structurally well-defined polysaccharide or related active oligosaccharide domains remains challenging. Herein, we describe an efficiently stereocontrolled approach for the first total synthesis of a unique pentasaccharide repeating unit containing four difficult-to-construct 1,2-cis-glycosidic linkages from the cell wall polysaccharide of Cutibacterium acnes C7. The features of our approach include: 1) acceptor-reactivity-controlled glycosylation to stereoselectively construct two challenging rare 1,2-cis-ManA2,3(NAc)2 (ß-2,3-diacetamido-2,3-dideoxymannuronic acid) linkages, 2) combination use of 6-O-tert-butyldiphenylsilyl (6-O-TBDPS)-mediated steric shielding effect and ether solvent effect to stereoselectively install a 1,2-cis-glucosidic linkage, 3) bulky 4,6-di-O-tert-butylsilylene (DTBS)-directed glycosylation to stereospecifically construct a 1,2-cis-galactosidic linkage, 4) stereoconvergent [2+2+1] and one-pot chemoselective glycosylation to rapidly assemble the target pentasaccharide. Immunological activity tests suggest that the pentasaccharide can induce the production of proinflammatory cytokine TNF-α in a dose-dependent manner.

Intradermal injection of Cutibacterium acnes and staphylococcus: A pustular acne-like murine model.

BACKGROUND: Skin 16S microbiome diversity analysis indicates that the Staphylococcus genus, especially Staphylococcus aureus (S. aureus), plays a crucial role in the inflammatory lesions of acne. However, current animal models for acne do not fully replicate human diseases, especially pustular acne, which limits the development of anti-acne medications. AIMS: The aim is to develop a mouse model for acne, establishing an animal model that more closely mimics the clinical presentation of pustular acne. This will provide a new research platform for screening anti-acne drugs and evaluating the efficacy of clinical anti-acne experimental treatments. METHODS: Building upon the existing combination of acne-associated Cutibacterium acnes (C. acnes) with artificial sebum, we will inject a mixture of S. aureus and C. acnes locally into the dermis in a 3:7 ratio. RESULTS: We found that the acne animal model with mixed bacterial infection better replicates the dynamic evolution process of human pustular acne. Compared to the infection with C. acnes alone, mixed bacterial infection resulted in pustules with a distinct yellowish appearance, resembling pustular acne morphology. The lesions exhibited redness, vascular dilation, and noticeable congestion, along with evident infiltration of inflammatory cells. This induced higher levels of inflammation, as indicated by a significant increase in the secretion of inflammatory factors such as IL-1ß and TNF-α. CONCLUSION: This model can reflect the clinical symptoms and development of human pustular acne, overcoming the limitations of animal models commonly used in basic research to study this situation. It provides support for foundational research and the development of new acne medications.

Brooklawnia propionicigenes sp. nov., a facultatively anaerobic, propionate-producing bacterium isolated from a methanogenic reactor treating waste from cattle farms.

Facultatively anaerobic bacterial strains were isolated from samples of a methanogenic reactor and, based on 16S rRNA gene sequences, found to be affiliated with the family Propionibacteriaceae in the phylum Actinomycetota. Four strains with almost-identical 16S rRNA gene sequences were comprehensively characterized. The most closely related species to the strains was Brooklawnia cerclae BL-34T (96.4 % sequence similarity). Although most of the phenotypic characteristics of the four strains were identical, distinct differences in some cellular and physiological properties were also detected. Cells of the strains were Gram-stain-positive, non-spore-forming, pleomorphic rods. The strains utilized carbohydrates and organic acids. The strains produced acetate, propionate and lactate from glucose, but the molar ratios of the products were variable depending on the strains. The strains grew at 10-40 °C (optimum at 35 °C) and pH 5.3-8.8 (optimum at pH 6.8-7.5.) The major cellular fatty acids of the strains were anteiso-C15 : 0, C15 : 0 and C15 : 0 dimethylacetal (as a summed feature). The major respiratory quinone was menaquinone MK-9(H4) and the diagnostic diamino acid in the peptidoglycan was meso-diaminopimelic acid. The genome size of the type strain (SH051T) was 3.21 Mb and the genome DNA G+C content was 65.7 mol%. Genes responsible for propionate production through the Wood-Werkman pathway were detected in the genome of strain SH051T. Based on the results of phylogenetic, genomic and phenotypic analyses of the novel strains, the name Brooklawnia propionicigenes sp. nov. is proposed to accommodate the four strains. The type strain of the novel species is SH051T (=NBRC 116195T=DSM 116141T).

Enzymatic synthesis of a skin active ingredient - glochidone by 3-ketosteroid dehydrogenase from Sterolibacterium denitrificans.

In this study, we applied AcmB2, sourced from Sterolibacterium denitrificans, to catalyze the oxidative dehydrogenation of 3-ketolupeol (lupenone), a derivative of lupeol, triterpene obtained from birch bark. This enzymatic Δ1-dehydrogenation catalyzed by AcmB2 yielded glochidone, a bioactive compound frequently obtained from medicinal plants like Salvia trichoclada and Maytenus boria. Glochidone is known for its broad biological activities, including antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic as well as acetylcholinesterase inhibition. Our research demonstrates >99% conversion efficiency with 100% regioselectivity of the reaction. The effective conversion to glochidone employed an electron acceptor e.g., potassium hexacyanoferrate III, in mild, environmentally friendly conditions: 8-16% 2-hydroxypropyl-ß-cyclodextrin, and 2-3% 2-methoxyethanol. AcmB2 reaction optimum was determined at pH 8.0 and 30 °C. Enzyme's biochemical attributes such as electron acceptor type, concentration and steroid substrate specificity were investigated. Among 4-, 5- and 6-ring steroid derivatives androst-4-en-3,17-dione and testosterone propionate were determined as the best substrates of AcmB2. Δ1-Dehydrogenation of substrates such as lupenone, diosgenone and 3-ketopetromyzonol was confirmed. We have assessed the antioxidant and rejuvenating characteristics of glochidone as an active component in formulations, considering its precursors, lupeol, and lupenone as well. Glochidone exhibited limited antioxidant and chelating capabilities compared to lupeol and reference compounds. However, it demonstrated robust rejuvenating properties, with a sirtuin induction level of 61.5 ± 1.87%, notably surpassing that of the reference substance, E-resveratrol (45.15 ± 0.09%). Additionally, glochidone displayed 26.5±0.67 and 19.41±0.76% inhibition of elastase and collagenase, respectively. The safety of all studied triterpenes was confirmed on skin reconstructed human Epidermis model. These findings provide valuable insights into the potential applications of glochidone in formulations aimed at addressing skin health concerns. This research presents the first example of an enzyme in the 3-ketosteroid dehydrogenase (KstD) family catalyzing the Δ1-dehydrogenation of a pentacyclic triterpene. We also explored structural differences between AcmB, AcmB2, and related KstDs pointing to G52 and P532 as potentially responsible for the unique substrate specificity of AcmB2. Our findings not only highlight the enzyme's capabilities but also present novel enzymatic pathways for bioactive compound synthesis.

High cell density sequential batch fermentation for enhanced propionic acid production from glucose and glycerol/glucose mixture using Acidipropionibacterium acidipropionici.

BACKGROUND: Propionic acid fermentation from renewable feedstock suffers from low volumetric productivity and final product concentration, which limits the industrial feasibility of the microbial route. High cell density fermentation techniques overcome these limitations. Here, propionic acid (PA) production from glucose and a crude glycerol/glucose mixture was evaluated using Acidipropionibacterium acidipropionici, in high cell density (HCD) batch fermentations with cell recycle. The agro-industrial by-product, heat-treated potato juice, was used as N-source. RESULTS: Using 40 g/L glucose for nine consecutive batches yielded an average of 18.76 ± 1.34 g/L of PA per batch (0.59 gPA/gGlu) at a maximum rate of 1.15 gPA/L.h, and a maximum biomass of 39.89 gCDW/L. Succinic acid (SA) and acetic acid (AA) were obtained as major by-products and the mass ratio of PA:SA:AA was 100:23:25. When a crude glycerol/glucose mixture (60 g/L:30 g/L) was used for 6 consecutive batches with cell recycle, an average of 35.36 ± 2.17 g/L of PA was obtained per batch (0.51 gPA/gC-source) at a maximum rate of 0.35 g/L.h, and reaching a maximum biomass concentration of 12.66 gCDW/L. The PA:SA:AA mass ratio was 100:29:3. Further addition of 0.75 mg/L biotin as a supplement to the culture medium enhanced the cell growth reaching 21.89 gCDW/L, and PA productivity to 0.48 g/L.h, but also doubled AA concentration. CONCLUSION: This is the highest reported productivity from glycerol/glucose co-fermentation where majority of the culture medium components comprised industrial by-products (crude glycerol and HTPJ). HCD batch fermentations with cell recycling are promising approaches towards industrialization of the bioprocess.

Cutibacterium namnetense osteosynthetic cervical spine infections: experience with two cases.

We report two uncommon cases of osteosynthetic cervical spine infection. Clinical patient features, microbiological strain characteristics, diagnostic methods, and treatment were analyzed. Both patients were male, and one had risk factors for surgical site infection. During surgery, perioperative samples were positive yielding an anaerobic microorganism identified as Cutibacterium namnetense by MALDI-TOF MS and confirmed by 16S rRNA/gyrB genes sequencing. All isolates were fully susceptible. C. namnetense osteosynthetic cervical spine infections are rare. Both cases were early surgical site infections. Bruker MALDI-TOF MS appears to be an excellent tool for rapid and accurate identification. Amoxicillin seems to be an option for the treatment.

Tessaracoccus caeni sp. nov., a novel member of Propionibacteriaceae isolated from activated sludge in Hefei, PR China.

A floc-forming bacterial strain, designated HF-7T, was isolated from the activated sludge of an industrial wastewater treatment plant in Hefei, PR China. Cells of this strain were Gram-stain-positive, catalase- and oxidase-negative, facultatively anaerobic, and rod-shaped. Growth occurred at 20-42 °C (optimum, 28 °C), at pH 5.5-10.5 (optimum, pH 7.5) and with 0-8.0 % (w/v) NaCl (optimum, 1 %). The major fatty acid was anteiso-C15 : 0. The polar lipid profile contained phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The DNA G+C content was 67 mol% from whole genomic sequence analysis. Based on the results of 16S rRNA gene sequence analysis, this strain should be assigned to the genus Tessaracoccus and is closely related to Tessaracoccus arenae CAU 1319T (95.87 % similarity), Tessaracoccus lapidicaptus IPBSL-7T (95.19 %) and Tessaracoccus bendigoensis Ben 106T (94.63 %) but separated from them by large distances in different phylogenetic trees. Based on whole genome analysis, the orthologous average nucleotide identity and in silico DNA-DNA hybridization values against two of the closest relatives were 75.21-76.50 % and 14.2-24.4 %, respectively. The phylogenetic, genotypic, phenotypic and chemotaxonomic data demonstrated that strain HF-7T could be distinguished from its phylogenetically related species and represents a novel species within the genus Tessaracoccus, for which the name Tessaracoccus caeni sp. nov. is proposed. The type strain is HF-7T (=KCTC 49959T=CCTCC AB 2023019T).

YTHDC1-Modified m6A Methylation of Hsa_circ_0102678 Promotes Keratinocyte Inflammation Induced by Cutibacterium acnes Biofilm through Regulating miR-146a/TRAF6 and IRAK1 Axis.

INTRODUCTION: CircRNAs are closely related to many human diseases; however, their role in acne remains unclear. This study aimed to determine the role of hsa_circ_0102678 in regulating inflammation of acne. METHODS: First, microarray analysis was performed to study the expression of circRNAs in acne. Subsequently, RNase R digestion assay and fluorescence in situ hybridization assay were utilized to confirm the characteristics of hsa_circ_0102678. Finally, qRT-PCR, Western blotting analysis, immunoprecipitation, luciferase reporter assay, circRNA probe pull-down assay, biotin-labeled miRNA pull-down assay, RNA immunoprecipitation assay, and m6A dot blot assay were utilized to reveal the functional roles of hsa_circ_0102678 on inflammation induced by C. acnes biofilm in human primary keratinocytes. RESULTS: Our investigations showed that the expression of hsa_circ_0102678 was significantly decreased in acne tissues, and hsa_circ_0102678 was a type of circRNAs, which was mainly localized in the cytoplasm of primary human keratinocytes. Moreover, hsa_circ_0102678 remarkably affected the expression of IL-8, IL-6, and TNF-α, which induced by C. acnes biofilm. Importantly, mechanistic studies indicated that the YTHDC1 could bind directly to hsa_circ_0102678 and promote the export of N6-methyladenosine-modified hsa_circ_0102678 to the cytoplasm. Besides, hsa_circ_0102678 could bind to miR-146a and sponge miR-146a to promote the expression of IRAK1 and TRAF6. CONCLUSION: Our findings revealed a previously unknown process by which hsa_circ_0102678 promoted keratinocyte inflammation induced by C. acnes biofilm via regulating miR-146a/TRAF6 and IRAK1 axis.

Avidumicin, a novel cyclic bacteriocin, produced by Cutibacterium avidum shows anti-Cutibacterium acnes activity.

The prevalence of antimicrobial-resistant Cutibacterium acnes in acne patients has increased owing to inappropriate antimicrobial use. Commensal skin bacteria may play an important role in maintaining the balance of the skin microbiome by producing antimicrobial substances. Inhibition of Cu. acnes overgrowth can prevent the development and exacerbation of acne vulgaris. Here, we evaluated skin bacteria with anti-Cu. acnes activity. Growth inhibition activity against Cu. acnes was tested using 122 strains isolated from the skin of healthy volunteers and acne patients. Comparative genomic analysis of the bacterium with or without anti-Cu. acnes activity was conducted. The anti-Cu. acnes activity was confirmed by cloning an identified gene cluster and chemically synthesized peptides. Cu. avidum ATCC25577 and 89.7% of the Cu. avidum clinical isolates (26/29 strains) inhibited Cu. acnes growth. The growth inhibition activity was also found against other Cutibacterium, Lactiplantibacillus, and Corynebacterium species, but not against Staphylococcus species. The genome sequence of Cu. avidum showed a gene cluster encoding a novel bacteriocin named avidumicin. The precursor protein encoded by avdA undergoes post-translational modifications, supposedly becoming a circular bacteriocin. The anti-Cu. acnes activity of avidumicin was confirmed by Lactococcus lactis MG1363 carrying avdA. The C-terminal region of the avidumicin may be essential for anti-Cu. acnes activity. A commensal skin bacterium, Cu. avidum, producing avidumicin has anti-Cu. acnes activity. Therefore, avidumicin is a novel cyclic bacteriocin with a narrow antimicrobial spectrum. These findings suggest that Cu. avidum and avidumicin represent potential alternative agents in antimicrobial therapy for acne vulgaris.

In Vivo Emergence of Dual Resistance to Rifampin and Levofloxacin in Osteoarticular Cutibacterium avidum.

Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of C. avidum ODRI, but oral rifampin is frequently used in combination with a fluoroquinolone following intravenous antibiotics. We describe the in vivo emergence of combined resistance to rifampin and levofloxacin in a C. avidum strain isolated from a patient with early-onset ODRI treated with debridement, antibiotic treatment, and implant retention (DAIR) using rifampin combined with levofloxacin as the oral treatment. Whole-genome sequencing of C. avidum isolates before and after antibiotic exposure confirmed strain identity and identified new mutations in rpoB and gyrA, leading to amino acid substitutions previously reported to be associated with resistance to rifampin (S446P) and fluoroquinolones (S101L), respectively, in other microbial agents, in the posttherapy isolate. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing a DAIR procedure for C. avidum ODRI and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens. IMPORTANCE In this study, we report for the first time the in vivo emergence of dual resistance to levofloxacin and rifampin in C. avidum isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.