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Nature Communications Dec 2023Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated...
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
Topics: Humans; Female; Animals; Mice; Hyaluronoglucosaminidase; Skin; Acne Vulgaris; Propionibacterium acnes; Amino Acids
PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8 -
The Journal of Investigative Dermatology Mar 1974
Review
Topics: Acne Vulgaris; Epithelial Cells; Epithelium; Fatty Acids; Gonadal Steroid Hormones; Models, Biological; Propionibacterium acnes; Sebaceous Glands; Sebum
PubMed: 4274209
DOI: 10.1111/1523-1747.ep12724280 -
MSphere Jan 2020Porphyrins are intermediate metabolites in the biosynthesis of vital molecules, including heme, cobalamin, and chlorophyll. Bacterial porphyrins are known to be... (Comparative Study)
Comparative Study
Porphyrins are intermediate metabolites in the biosynthesis of vital molecules, including heme, cobalamin, and chlorophyll. Bacterial porphyrins are known to be proinflammatory, with high levels linked to inflammatory skin diseases. species are dominant skin commensals and play essential roles in defending against pathogens and in triggering an inflammatory response. To better understand how the inflammatory potential of the skin microbiome may vary depending on its propionibacterial composition, we compared the production levels of porphyrins among , , , and strains. We found that porphyrin production varied among these species, with type I strains producing significantly larger amounts of porphyrins than type II and III strains and other species. strains that are highly associated with the common skin condition acne vulgaris responded to vitamin B supplementation with significantly higher porphyrin production. In contrast, vitamin B supplementation had no effect on the porphyrin production of health-associated strains and other propionibacteria. We observed low-level porphyrin production in most strains harboring the repressor gene, with the exception of strains belonging to type I clades IB-3 and IC. Our findings shed light on the proinflammatory potential of distinct phylogenetic lineages of as well as other resident skin propionibacteria. We demonstrate that the overall species and strain composition is important in determining the metabolic output of the skin microbiome in health and disease. Porphyrins are a group of metabolites essential to the biosynthesis of heme, cobalamin, and chlorophyll in living organisms. Bacterial porphyrins can be proinflammatory, with high levels linked to human inflammatory diseases, including the common skin condition acne vulgaris. Propionibacteria are among the most abundant skin bacteria. Variations in propionibacteria composition on the skin may lead to different porphyrin levels and inflammatory potentials. This study characterized porphyrin production in all lineages of , the most dominant skin , and other resident skin propionibacteria, including , , and We revealed that type I strains produced significantly more porphyrins than did type II and III strains and other species. The findings from this study shed light on the proinflammatory potential of the skin microbiome and can be used to guide the development of effective acne treatments by modulating the skin microbiome and its metabolic activities.
Topics: Humans; Microbiota; Phylogeny; Porphyrins; Propionibacteriaceae; Propionibacterium; Propionibacterium acnes; Skin
PubMed: 31941813
DOI: 10.1128/mSphere.00793-19 -
BioMed Research International 2013
Topics: Humans; Propionibacterium acnes; Skin Diseases, Bacterial
PubMed: 24455697
DOI: 10.1155/2013/493564 -
BioMed Research International 2013The role of Propionibacterium acnes in acne and in a wide range of inflammatory diseases is well established. However, P. acnes is also responsible for infections... (Review)
Review
The role of Propionibacterium acnes in acne and in a wide range of inflammatory diseases is well established. However, P. acnes is also responsible for infections involving implants. Prolonged aerobic and anaerobic agar cultures for 14 days and broth cultures increase the detection rate. In this paper, we review the pathogenic role of P. acnes in implant-associated infections such as prosthetic joints, cardiac devices, breast implants, intraocular lenses, neurosurgical devices, and spine implants. The management of severe infections caused by P. acnes involves a combination of antimicrobial and surgical treatment (often removal of the device). Intravenous penicillin G and ceftriaxone are the first choice for serious infections, with vancomycin and daptomycin as alternatives, and amoxicillin, rifampicin, clindamycin, tetracycline, and levofloxacin for oral treatment. Sonication of explanted prosthetic material improves the diagnosis of implant-associated infections. Molecular methods may further increase the sensitivity of P. acnes detection. Coating of implants with antimicrobial substances could avoid or limit colonization of the surface and thereby reduce the risk of biofilm formation during severe infections. Our understanding of the role of P. acnes in human diseases will likely continue to increase as new associations and pathogenic mechanisms are discovered.
Topics: Animals; Anti-Bacterial Agents; Gram-Positive Bacterial Infections; Host-Pathogen Interactions; Humans; Propionibacterium acnes; Prostheses and Implants
PubMed: 24308006
DOI: 10.1155/2013/804391 -
Respiratory Investigation Jun 2013Propionibacterium acnes is the only microorganism isolated from sarcoid lesions by bacterial culture. Numerous P. acnes genomes are found in lymph node samples from... (Review)
Review
Propionibacterium acnes is the only microorganism isolated from sarcoid lesions by bacterial culture. Numerous P. acnes genomes are found in lymph node samples from Japanese and European patients with sarcoidosis, whereas a few genomes are found in some non-sarcoid samples. The high frequency and specificity of detecting P. acnes within sarcoid granulomas suggests that this indigenous bacterium causes granuloma formation in many patients with sarcoidosis. P. acnes is the most common commensal bacterium in the lungs and lymph nodes. Occasional detection of P. acnes in non-granulomatous areas of these organs from non-sarcoid patients suggests that host factors are more critical than agent factors in the etiology of sarcoidosis. A particular protein, i.e., trigger factor, from P. acnes causes a cellular immune response only in sarcoid patients. The P. acnes trigger-factor protein induces pulmonary granulomas in mice sensitized with the protein and adjuvant, but only in those with latent P. acnes infection in their lungs. Eradication of P. acnes by antibiotics prevents the development of granulomas in this experimental model. P. acnes can cause latent infection in the lung and lymph nodes and persists in a cell wall-deficient form. The dormant form is endogenously activated under certain conditions and proliferates at the site of latent infection. In patients with P. acnes hypersensitivity, granulomatous inflammation is triggered by intracellular proliferation of the bacterium. Proliferating bacteria may escape granulomatous isolation, spreading to other organs. Latent P. acnes infection in systemic organs can be reactivated by another triggering event, leading to systemic sarcoidosis.
Topics: Gram-Positive Bacterial Infections; Humans; Propionibacterium acnes; Sarcoidosis
PubMed: 23790733
DOI: 10.1016/j.resinv.2013.01.001 -
Clinical Microbiology Reviews Jul 2018The recent description of the genus has altered the taxonomy of species. These organisms still belong to the genera of the skin coryneform group, and the most-studied... (Review)
Review
The recent description of the genus has altered the taxonomy of species. These organisms still belong to the genera of the skin coryneform group, and the most-studied species remains . is also a known skin commensal. This underrecognized microorganism can, however, act as a pathogen after bacterial seeding and can be considered opportunistic, causing either superficial or deep/invasive infections. It can cause numerous infections, including but not limited to breast infections, skin abscesses, infective endocarditis, and device-related infections. The ecological niche of is clearly different from that of other members of the genus: it is found in the axillary region or at wet sites rather than in dry, exposed areas, and the number of microorganisms increases during puberty. Historically, it has been used for its ability to modulate the immune response and for its antitumor properties. Conventional microbial culture methods and identification processes allow for its accurate identification and characterization. Thanks to the modern omics tools used for phylogenomic approaches, understanding pathogenesis (including host-bacterium interactions and virulence factor characterization) is becoming easier, allowing for more thorough molecular characterization. These analyses have revealed that causes diverse diseases mediated by multiple virulence factors. The recent genome approach has revealed specific genomic regions within this species that are involved in adherence and biofilm formation as well as fitness, survival, and defense functions. Numerous regions show the presence of phages and horizontal gene transfer. remains highly sensitive to a broad spectrum of antibiotics, such as β-lactams, fluoroquinolones, macrolides, and rifampin, although erythromycin and clindamycin resistance has been described. A long-term treatment regimen with a combination of antibiotics is required to successfully eliminate the remaining adherent bacteria, particularly in the case of deep infections after debridement surgery.
Topics: Actinomycetales Infections; Anti-Bacterial Agents; Humans; Phylogeny; Propionibacterium
PubMed: 29848774
DOI: 10.1128/CMR.00064-17 -
Scientific Reports Jun 2021Staphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage...
Staphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage difference between electrodes. Production of electron was validated by a Ferrozine assay. The anti-Cutibacterium acnes (C. acnes) activity of electrogenic S. epidermidis was assessed in vitro and in vivo. The voltage change (~ 4.4 mV) reached a peak 60 min after pipetting S. epidermidis plus 2% PEG-8 Laurate onto anodes. The electricity produced by S. epidermidis caused significant growth attenuation and cell lysis of C. acnes. Intradermal injection of C. acnes and S. epidermidis plus PEG-8 Laurate into the mouse ear considerably suppressed the growth of C. acnes. This suppressive effect was noticeably reversed when cyclophilin A of S. epidermidis was inhibited, indicating the essential role of cyclophilin A in electricity production of S. epidermidis against C. acnes. In summary, we demonstrate for the first time that skin S. epidermidis, in the presence of PEG-8 Laurate, can mediate cyclophilin A to elicit an electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the onset of acne vulgaris.
Topics: Acne Vulgaris; Animals; Antibiosis; Bacterial Proteins; Coculture Techniques; Culture Media; Cyclophilin A; Disease Models, Animal; Ear; Electricity; Electrodes; Female; Gene Expression; Laurates; Mice; Mice, Inbred ICR; Polyethylene Glycols; Propionibacteriaceae; Skin; Staphylococcus epidermidis; Surface-Active Agents
PubMed: 34099817
DOI: 10.1038/s41598-021-91398-7 -
Nature Communications Feb 2023Acne vulgaris is a common neutrophil-driven inflammatory skin disorder in which Cutibacterium acnes (C. acnes) is known to play a key role. For decades, antibiotics have...
Acne vulgaris is a common neutrophil-driven inflammatory skin disorder in which Cutibacterium acnes (C. acnes) is known to play a key role. For decades, antibiotics have been widely employed to treat acne vulgaris, inevitably resulting in increased bacterial antibiotic resistance. Phage therapy is a promising strategy to combat the growing challenge of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria. Herein, we explore the feasibility of phage therapy against C. acnes. Eight novel phages, isolated in our laboratory, and commonly used antibiotics eradicate 100% of clinically isolated C. acnes strains. Topical phage therapy in a C. acnes-induced acne-like lesions mouse model affords significantly superior clinical and histological scores. Moreover, the decrease in inflammatory response was reflected by the reduced expression of chemokine CXCL2, neutrophil infiltration, and other inflammatory cytokines when compared with the infected-untreated group. Overall, these findings indicate the potential of phage therapy for acne vulgaris as an additional tool to conventional antibiotics.
Topics: Animals; Mice; Phage Therapy; Acne Vulgaris; Anti-Bacterial Agents; Skin; Drug Resistance, Bacterial; Propionibacterium acnes
PubMed: 36813793
DOI: 10.1038/s41467-023-36694-8 -
Trends in Microbiology Jun 2015The human gut contains a highly diverse microbial community that is essentially an open ecosystem, despite being deeply embedded within the human body. Food-associated... (Review)
Review
The human gut contains a highly diverse microbial community that is essentially an open ecosystem, despite being deeply embedded within the human body. Food-associated fermentative bacteria, including probiotics, are major sources of ingested bacteria that may temporarily complement resident microbial communities, thus forming part of our transient microbiome. Here, we review data on the fate and activity of ingested bacteria and, in particular, lactobacilli and bifidobacteria in the gastrointestinal (GI) tract and their impact on the composition and metabolism of the gut microbiome with a focus on data from clinical studies. In addition, we discuss the mechanisms involved and the potential impact on the host's health.
Topics: Bacterial Physiological Phenomena; Bifidobacterium; Clinical Trials as Topic; Diet; Eating; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Lactobacillus; Microbial Interactions; Probiotics; Propionibacteriaceae
PubMed: 25840765
DOI: 10.1016/j.tim.2015.03.002