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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 -
Archivio Italiano Di Urologia,... Mar 2022Propionibacterium acnes has been implicated in the pathogenesis of prostate disease as acute and chronic prostatic inflammation, benign prostatic hyperplasia and...
OBJECTIVE
Propionibacterium acnes has been implicated in the pathogenesis of prostate disease as acute and chronic prostatic inflammation, benign prostatic hyperplasia and prostate cancer although it should still be clarified if Propionibacterium acnes (P. acnes) is a commensal or accidental prostate pathogen. Aiming to evaluate the pathogenic potential for genitourinary tract of Propionibacterium acnes, we investigated the frequency of P. acnes genome in urine or semen samples from men with recurrent symptoms of urinary infection and negative testing for the most common urinary tract pathogens and sexually transmitted infections (STI) agents as Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum.
MATERIALS AND METHODS
The DNA extracted from urine and semen samples was analyzed for evaluating the P. acnes genome presence by real-time polymerase chain reaction (PCR). Infections were treated with vancomycin and cephalosporins antibiotics and then the search for the P.acnes genome by realtime PCR was repeated.
RESULTS
The P. acnes qualitative real-time PCR revealed the genome in 73 out of 159 samples examined (108 urine and 51 semen). After antibiotic therapy, P. acnes was never detected.
CONCLUSIONS
These results suggested that P. acnes genome determination should be performed in cases of chronic inflammation in the urinary tract to identify an unknown potential pathogen of genitourinary tract.
Topics: Humans; Male; Mycoplasma genitalium; Mycoplasma hominis; Propionibacterium acnes; Semen; Ureaplasma urealyticum
PubMed: 35352527
DOI: 10.4081/aiua.2022.1.62 -
Dermatology and Therapy Mar 2019Acne vulgaris is the most common dermatological disorder worldwide. It is a multifactorial disease that involves increased sebum production, hyperkeratinization of the... (Review)
Review
Acne vulgaris is the most common dermatological disorder worldwide. It is a multifactorial disease that involves increased sebum production, hyperkeratinization of the pilosebaceous unit, Propionibacterium acnes (Cutibacterium acnes) colonization, and inflammation. The human skin microbiome hosts a wide variety of microorganisms, including bacteria, viruses, and fungi. A delicate balance of these microorganisms is essential for the barrier function of the skin. Propionibacterium acnes represents nearly 90% of the human skin microbiome of healthy adults. Acne is a chronic recurrent disease that requires long-lasting treatment, which has led to the emergence of antibiotic resistance. New alternatives to traditional therapy are emerging, including antimicrobial peptides, natural engineered antibodies, and bacteriophages. Bacteriophages have been shown to play a role in human skin health and disease. There is evidence supporting phage therapy in many types of skin infections. P. acnes bacteriophages have been isolated and characterized. However, only a few in vitro studies have tested the ability of bacteriophages to kill P. acnes. Furthermore, there is no evidence on bacteriophage therapy in the treatment of acne in humans. In this review, we summarize the most recent evidence regarding P. acnes bacteriophages and the potential role of these bacteriophages in the treatment of acne. Further research on this field will provide the evidence to use phage therapy to decrease rates of antibiotic resistance and restore antibiotic susceptibility of P. acnes.
PubMed: 30539425
DOI: 10.1007/s13555-018-0275-9 -
International Journal of Molecular... May 2023The emergence of multidrug-resistant (MDR) bacteria has risen rapidly, leading to a great threat to global public health. A promising solution to this problem is the...
The emergence of multidrug-resistant (MDR) bacteria has risen rapidly, leading to a great threat to global public health. A promising solution to this problem is the exploitation of phage endolysins. In the present study, a putative N-acetylmuramoyl-L-alanine type-2 amidase (NALAA-2, EC 3.5.1.28) from bacteriophage PAC1 was characterized. The enzyme (Ami1) was cloned into a T7 expression vector and expressed in BL21 cells. Kinetics analysis using turbidity reduction assays allowed the determination of the optimal conditions for lytic activity against a range of Gram-positive and negative human pathogens. The peptidoglycan degradation activity of Ami1 was confirmed using isolated peptidoglycan from . The antibacterial activity of Ami1 was investigated using live cells growing on agar plates. Two engineered variants of Ami1 were designed by fusion to its N-terminus two short antimicrobial peptides (AMPs). One AMP was selected by searching the genomes of bacteriophages using bioinformatics tools, whereas the other AMP sequence was selected from the antimicrobial peptide databases. Both engineered variants exhibited improved lytic activity towards and the enterococci species and . The results of the present study suggest that Ami1 is a new antimicrobial agent and provide proof of concept that bacteriophage genomes are a rich source of AMP sequences that can be further exploited for designing novel or improved endolysins.
Topics: Humans; Propionibacterium acnes; Peptidoglycan; Escherichia coli; Endopeptidases; Siphoviridae; Bacteriophages; Anti-Bacterial Agents
PubMed: 37239874
DOI: 10.3390/ijms24108523 -
Anais Brasileiros de Dermatologia 2017Acne fulminans is a rare and severe variant of acne. In Brazilian medical journals, cases are infrequently reported, confirming its rarity. We followed five young male...
Acne fulminans is a rare and severe variant of acne. In Brazilian medical journals, cases are infrequently reported, confirming its rarity. We followed five young male patients with this severe variant of cutaneous lesions, accompanied by also severe systemic symptoms: fever, anorexia, weight loss, and arthralgia. All had a good response to corticosteroids (prednisone), but had significant scarring.
Topics: Acne Vulgaris; Adolescent; Arthralgia; Disease Progression; Fever; Glucocorticoids; Humans; Male; Necrosis; Prednisone; Propionibacterium acnes; Severity of Illness Index; Superantigens; Young Adult
PubMed: 29267432
DOI: 10.1590/abd1806-4841.20176546 -
Orthopaedic Journal of Sports Medicine Feb 2022Equipment used to guide surgical incisions has been shown to be a source of bacterial contamination during surgery.
BACKGROUND
Equipment used to guide surgical incisions has been shown to be a source of bacterial contamination during surgery.
PURPOSE/HYPOTHESIS
To compare the culture-positive rates of sterile marking pens used before and after skin preparation for shoulder surgery. It was hypothesized that there will be no difference in culture-positive rates from marking pens used after skin preparation compared with before skin preparation.
STUDY DESIGN
Controlled laboratory study.
METHODS
Overall, 43 consecutive patients undergoing elective shoulder surgery were enrolled prospectively into this study. Each patient provided 2 samples: study pens (from marking the surgical site incision after skin preparation) and positive control pens (from marking the surgical site incision before skin preparation). In addition, there were 43 negative control pens evaluated (straight from the packaging without any patient contact). Cultures were evaluated at 4 and 21 days, and all positive cultures were further evaluated for speciation, if able. Standard descriptive summaries and Fisher exact tests were used to compare the study samples.
RESULTS
The average age of the 43 patients was 54 years (range, 18-76 years). There were 29 (67%) female patients, and 30 (70%) procedures were on the right shoulder. Of the 43 procedures performed, 29 (67.4%) were arthroscopic, 12 (27.9%) were open, and 2 (4.7%) were closed. Of the 43 study pens, 1 culture was positive for (2.3%). Of the 43 positive control pens, 2 cultures were positive for bacterial growth (4.7%): and Gram-positive bacilli (no speciation could be obtained). Of the 43 negative control pens, none of the cultures were positive for bacterial growth (0%). There was no statistical difference in the culture-positive rate between the study pens and the positive or negative control pens ( ≥ .999).
CONCLUSION
Study results indicated that sterile surgical marking pens used to plan incisions and to outline anatomic landmarks did not have a higher culture-positive rate compared with pens used on unprepared skin or pens straight from the packaging.
CLINICAL RELEVANCE
As a precaution, sterile surgical marking pens should be discarded after use on the skin surface and not placed on the sterile field.
PubMed: 35187182
DOI: 10.1177/23259671211062225 -
Frontiers in Cellular and Infection... 2017This review discusses the biology and behavior of (), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and... (Review)
Review
This review discusses the biology and behavior of (), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and severity of disease. More specifically, we discuss the ability of to invade and persist in epithelial cells and circulating macrophages to subsequently induce bouts of sarcoidosis, low-grade inflammation and metastatic cell growth in the prostate gland. Finally, we discuss the possibility of infiltrating the brain parenchyma to indirectly contribute to pathogenic processes in neurodegenerative disorders such as those observed in Parkinson's disease (PD).
Topics: Animals; Epithelial Cells; Host-Pathogen Interactions; Humans; Macrophages; Male; Neurodegenerative Diseases; Propionibacterium acnes; Prostate; Sarcoidosis; Skin
PubMed: 28352613
DOI: 10.3389/fcimb.2017.00081 -
The Journal of Medical Investigation :... 2020Propionibacterium acnes (P. acnes) is part of the normal flora of human skin, oral cavity, intestinal tract and external ear canal. However, breach in the mucosa as well... (Review)
Review
Propionibacterium acnes (P. acnes) is part of the normal flora of human skin, oral cavity, intestinal tract and external ear canal. However, breach in the mucosa as well as ruptured annulus fibrosus provide favorable pathway for P. acnes to nucleus pulposus where it can proliferate under anaerobic condition. In past two decades many authors have identified P. acnes in routine culture of discs. There studies showed that almost 50% of discs cultured were positive for various organism, and in vast majority of culture positive disc, P. acnes was the primary organism isolated. However, there are few studies that refute the hypothesis that P. acnes has a role in pathogenesis of Modic type 1 changes. Identification of P. acnes in culture indicates the infective patho-mechanism in the pathogenesis of Modic type 1 changes, which may be ameable to antibiotic treatment. However, it is still difficult to identify which subset of these patients (patients with low back pain with type 1 Modic change) are infective in nature. Further investigation and more clinical trails will be required for clear identification of the infective subgroup among low back patient in general. J. Med. Invest. 67 : 21-26, February, 2020.
Topics: Anti-Bacterial Agents; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Low Back Pain; Propionibacterium acnes
PubMed: 32378611
DOI: 10.2152/jmi.67.21 -
JCI Insight Mar 2019Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris....
Genomic studies revealed the existence of health- and acne-associated P. acnes strains and suggested novel approaches for broadening understanding of acne vulgaris. However, clinical association of P. acnes with disease or health has yet to be corroborated experimentally. Current animal models of acne do not closely mimic human disease and have unclear translational value. We have developed a murine model of acne by combining P. acnes inoculation with topical application of a synthetic human sebum. We showed that human sebum promoted persistence of intradermally injected P. acnes with little loss of viability after 1 week and permitted use of more physiologic inoculums. Application of acne-associated P. acnes RT4/5 strains led to development of moderate to severe skin pathology compared with application of health-associated type II P. acnes strains (RT2/6). RT4/5 P. acnes strains uniformly induced higher levels of KC (IL-8), IL-1α, IL-1β, and IL-6 in vitro and in vivo compared with type II P. acnes strains. Overall, our data provide immunopathologic corroboration of health and disease association of clinical P. acnes strains and inform on a platform to query putative virulence factors uncovered by genomic studies.
Topics: Acne Vulgaris; Animals; Bone Marrow Cells; Cell Line; Disease Models, Animal; Female; Gram-Positive Bacterial Infections; Humans; Interleukin-1alpha; Interleukin-6; Interleukin-8; Mice; Mice, Inbred C57BL; Propionibacterium acnes; Skin; Virulence Factors
PubMed: 30843879
DOI: 10.1172/jci.insight.124687 -
International Journal of Biological... 2022Acne vulgaris is a common skin disease, affecting over 80% of adolescents. Inflammation is known to play a central role in acne development. Here, we aimed to...
Acne vulgaris is a common skin disease, affecting over 80% of adolescents. Inflammation is known to play a central role in acne development. Here, we aimed to investigate the role of the central clock gene in acne-associated inflammation in mice. To this end, mice were injected intradermally with () to induce acne-associated skin inflammation. We found that and its target genes and were down-regulated in the skin of -treated mice, suggesting a role of in the condition of acne. Supporting this, -deleted or jet-lagged mice showed exacerbated -induced inflammation in the skin. Regulation of -induced inflammation by was further confirmed in RAW264.7 cells and primary mouse keratinocytes. Transcriptomic and protein expression analyses suggested that regulated -induced inflammation via the NF-κB/NLRP3 axis, which is known to be repressed by REV-ERBα (a direct target of BMAL1). Moreover, loss of in mice exacerbated -induced inflammation. In addition, silencing attenuated the inhibitory effects of on -induced inflammation. knockdown failed to modulate -induced inflammation in -silenced cells. It was thus proposed that restrained -induced skin inflammation via its target REV-ERBα, which acts on the NF-κB/NLRP3 axis to repress inflammation. In conclusion, disruption is identified as a potential pathological factor of acne-associated inflammation. The findings increase our understanding of the crosstalk between skin clock and acne and suggest targeting circadian rhythms as a promising approach for management of acne.
Topics: ARNTL Transcription Factors; Acne Vulgaris; Animals; Inflammation; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Nuclear Receptor Subfamily 1, Group D, Member 1; Propionibacterium acnes
PubMed: 35414779
DOI: 10.7150/ijbs.71719