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  • 1.
    Alexeyev, O. A.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jahns, A. C.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sampling and detection of skin Propionibacterium acnes: Current status2012In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, no 5, p. 479-483Article, review/survey (Refereed)
    Abstract [en]

    A connection between acne vulgaris and Propionibacterium acnes has long been suggested. Over the years, several human skin microbiota sampling methods have been evolved and applied, e.g. swab, scrape, extraction techniques including cyanoacrylate gel sampling as well as punch biopsy. Collected samples have been processed following various methodologies ranging from culture studies to probe labelling and molecular analysis. Direct visualization techniques have recently shown the existence of anatomically distinct skin P acnes populations: epidermal and follicular. P. acnes biofilms appear to be a common phenomenon. Current sampling approaches target different skin populations of P. acnes and the presence of microbial biofilms can influence the retrieval of P. acnes. The anatomical considerations must be taken into account while interpreting microbiological data. (C) 2012 Elsevier Ltd. All rights reserved.

  • 2.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bacterial landscape of human skin: seeing the forest for the trees2013In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 22, no 7, p. 443-446Article in journal (Refereed)
    Abstract [en]

    Skin harbours large communities of colonizing bacteria. The same bacterial species can exist in different physiological states: viable, dormant, non-viable. Each physiological state can have a different impact on skin health and disease. Various analytical methodologies target different physiological states of bacteria, and this must be borne in mind while interpreting microbiological tests and drawing conclusions about possible cause-effect relationships.

  • 3.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Is it time to switch on or off the green light for ultraviolet-induced red fluorescence as a surrogate marker for Propionibacterium acnes in vivo?2017In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 26, no 1, p. 26-27Article in journal (Refereed)
  • 4.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Aava, Birgitta
    Skoglig Zooekologi, SLU, Umeå.
    Palo, Thomas
    Skoglig Zooekologi, SLU, Umeå.
    Settergren, Bo
    Tärnvik, Arne
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    A minority of seropositive wild bank voles (Clethrionomys glareolus) show evidence of current Puumala virus infection1998In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 121, no 2, p. 419-425Article in journal (Refereed)
    Abstract [en]

    Bank voles (Clethrionomys glareolus) serve as the reservoir for Puumala (PUU) virus, the aetiologic agent of nephropathia epidemica. The animals are believed to be persistently infected and the occurrence of serum antibodies is usually taken as an evidence of active infection. We found serum antibodies to PUU virus in 42 of 299 wild bank voles captured in a PUU virus endemic area. PUU virus RNA was demonstrated in lung specimens of 11 of these 42 animals and in 2 of them antigen was also found. Thus in the lungs of 31 of 42 seropositive animals neither PUU virus RNA nor antigen was detected. In 2 of 257 seronegative animals, lung specimens showed presence of PUU virus antigen and RNA. Isolation of PUU virus from lung tissue was successful in all 4 antigen-positive bank voles but in none of 16 tested antigen-negative animals. In conclusion, only a minority of bank voles with serum antibodies to PUU virus showed evidence of current infection.

  • 5.
    Alexeyev, Oleg A.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dekio, I.
    Layton, A. M.
    Li, H.
    Hughes, H.
    Morris, T.
    Zouboulis, C. C.
    Patrick, S.
    Why we continue to use the name Propionibacterium acnes2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 179, no 5, p. 1227-1227Article in journal (Other (popular science, discussion, etc.))
  • 6.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, Ruta
    Palmer, Ruth H
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    McDowell, Andrew
    Patrick, Sheila
    Zouboulis, Christos
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Pattern of tissue invasion by Propionibacterium acnes in acne vulgaris2012In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 67, no 1, p. 63-66Article in journal (Refereed)
  • 7.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zouboulis, Christos C
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Shooting at skin propionibacterium acnes: to be or not to be on target2013In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 133, no 9, p. 2292-2294Article in journal (Refereed)
  • 8.
    Alexeyev, Oleg
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh, Johanna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiklund, Fredrik
    Grönberg, Henrik
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 9, p. 1127-1133Article in journal (Refereed)
    Abstract [en]

    Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).

    Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.

    Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).

    Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.

  • 9.
    Alexeyev, Oleg
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Is there evidence for a role of Propionibacterium acnes in prostatic disease?2009In: Urology, ISSN 1527-9995, Vol. 73, no 2, p. 220-224Article in journal (Refereed)
  • 10.
    Bergh Drott, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergström, Patrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells2010In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 10, p. 126-Article in journal (Refereed)
    Abstract [en]

    Background: The immune stimulating bacterium Propionibacterium acnes is a frequent colonizer of benign and malignant prostate tissue. To understand the pathogenesis of the earliest phase of this infection, we examined the P. acnes triggered immune response in cultivated prostate epithelial cells.

    Results: Prostate epithelial cells are triggered to secrete IL-6, IL-8 and GM-CSF when infected with P. acnes. The secretion of cytokines is accompanied by NFκB related upregulation of the secreted cytokines as well as several components of the TLR2-NFκB signaling pathway.

    Conclusions: P. acnes has potential to trigger a strong immune reaction in the prostate glandular epithelium. Upon infection of prostate via the retrograde urethral route, the induced inflammatory reaction might facilitate bacterial colonization deeper in the prostate tissue where persistent inflammation may impact the development of prostate diseases as hyperplasia and/or malignancy.

  • 11.
    Bergh, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gustavsson, C
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Alexeyev, Olog
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    No link between viral findings in the prostate and subsequent cancer development2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, no 1, p. 137-139Article in journal (Refereed)
    Abstract [en]

    In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

  • 12.
    Eilers, Hinnerk
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion2016In: Journal of drugs in dermatology, ISSN 1545-9616, Vol. 15, no 6, p. 778-781Article in journal (Refereed)
    Abstract [en]

    Background: P. acnes biofilms are emerging topics in acne vulgaris pathogenesis and may be responsible for antibiotic tolerance. Objective: To investigate the efficacy of GT peptide 10 either alone or in combination with triethyl citrate (TEC) in in vitro model of P acnes biofilm. Methods: Six-day-old P acnes biofilms were treated with various concentrations of these substances and biofilm dispersion and cell viability were monitored. Results: A 24-hour exposure of preformed biofilms to a combination of GT peptide 10/TEC led to killing of up to 92% of bacterial cells inside the biofilm. Neither the single substance nor the combination of both substances affected the biofilm integrity or resulted in biofilm dispersal. Conclusions: A combination of GT peptide 10/TEC shows antibacterial effects in in vitro model of P. acnes biofilm.

  • 13.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Larsson, Pär
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wikberg, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Cancer-associated fecal microbial markers in colorectal cancer detection2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

  • 14.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Direct visualization of a gravid Demodex mite in human skin biopsy2012In: Journal der Deutschen Dermatologischen Gesellschaft, ISSN 1610-0379, E-ISSN 1610-0387, Vol. 10, no 5, p. 358-359Article in journal (Refereed)
  • 15.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Microbial colonization of normal skin: Direct visualization of 194 skin biopsies2016In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 38, p. 47-49Article in journal (Refereed)
    Abstract [en]

    Recent genetic studies have suggested the presence of numerous microbial species on and in the skin. We characterised microbial colonization of a large collection of skin biopsies from 194 healthy subjects by fluorescence assay. Forty per cent of all biopsies did not show any evidence for microbial colonization. Propionibacterium acnes was the sole predominant bacterial species in both sebaceous and non-sebaceous areas. Non- P. acnes species were present in approximately 30% of all colonized samples.. Only hair follicles and stratum corneum were colonized. Understanding of cutaneous microbiota requires validation from a variety of approaches and techniques.

  • 16.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Three dimensional distribution of Propionibacterium acnes biofilms in human skin2014In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 23, no 9, p. 687-689Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is regarded as a common member of the human skin microbiota, often occurring in biofilms. Little is known about the size of bacterial biofilms in hair follicles as a few sections of biopsy tissue are routinely evaluated. Transversal sectioning provides a better opportunity for histological analyses of hair follicles which can be followed through the different morphological levels. Direct visualization of P.acnes biofilms in hundreds of consecutive sections allowed insight into the 3D distribution in human hair follicles as well as investigating the depth of biofilm distribution within hair follicles. Four distinct colonization patterns of P.acnes biofilms were revealed. Results have shown that an individual P.acnes biofilm can spread for 1900m in a terminal hair follicle. This information can be of help while designing potential antibiofilm treatment.

  • 17.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Eilers, Hinnerk
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Transcriptomic analysis of Propionibacterium acnes biofilms in vitro2016In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 42, p. 111-118Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a well-known commensal of the human skin connected to acne vulgaris and joint infections. It is extensively studied in planktonic cultures in the laboratory settings but occurs naturally in biofilms. In this study we have developed an in vitro biofilm model of P. acnes and studied growth features, matrix composition, matrix penetration by fluorescent-labeled antibiotics as well as gene expression. Antibiotic susceptibility of biofilms was studied and could be enhanced by increased glucose concentrations. Biofilm cells were characterized by up-regulated stress-induced genes and up regulation of genes coding for the potential virulence-associated CAMP factors. P. acnes can generate persister cells showing a reversible tolerance to 50 fold MIC of common antibiotics.

  • 18.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Eilers, Hinnerk
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, R.
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Propionibacterium species and follicular keratinocyte activation in acneic and normal skin2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 4, p. 981-987Article in journal (Refereed)
    Abstract [en]

    Background The pathogenesis of acne vulgaris is multifactorial with increased sebum production, alteration in the quality of sebum lipids, dysregulation of the hormone microenvironment, follicular hyperkeratinization and Propionibacterium acnes-driven inflammation as major contributory factors. Hyperproliferation of keratinocytes is believed to contribute to hypercornification and eventually leads to comedone development. While the distribution of P. acnes is relatively well documented in acneic and healthy skin, little is known about P. granulosum and P. avidum.

    Objectives To visualize directly the three major Propionibacterium in 117 control and 26 acneic skin samples. In addition, keratinocyte proliferation was evaluated.

    Methods Propionibacteria were visualized by immunofluorescence microscopy, and keratinocyte proliferation was assessed by Ki67, keratin (K) 16 and p63 immunochemistry.

    Results P. acnes was identified in 68 samples (48%), while P. granulosum was identified in 12 (8%) samples; P. avidum was not detected at all. Unexpectedly, acne samples did not show higher keratinocyte proliferation than controls, nor was there any association between bacterial colonization and expression of Ki67/K16/p63.

    Conclusions Our findings do not support earlier notions of follicular keratinocyte hyperproliferation as a cause of ductal hypercornification in acneic facial skin. Further studies on the mechanisms underlying hypercornification in acne pathogenesis are needed.

  • 19.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Palmer, Ruth H
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Spatial distribution of bacterial-fungal communities in facial skin2013In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 70, no 1, p. 71-73Article in journal (Refereed)
  • 20.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine.
    Berg, Johanna
    Umeå University, Faculty of Medicine.
    Jonsson, Rebecca
    Umeå University, Faculty of Medicine.
    McDowell, Andrew
    Patrick, Sheila
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Palmer, Ruth H.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Microbiology of folliculitis: a histological study of 39 cases2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    Folliculitis is a common inflammatory skin syndrome. Several microbial organisms have been put forward as causative agents, but few studies visualized microbes directly in inflamed hair follicles. This retrospective study investigated bacterial and fungal colonization of inflamed hair follicles in patients with clinically diagnosed non-infectious folliculitis. Skin biopsies from 39 folliculitis patients and 27 controls were screened by fluorescence in situ hybridization (FISH) using broad-range bacterial and fungal probes and by immunofluorescence microscopy using a monoclonal antibody towards Gram-positive bacteria. Specific monoclonal and polyclonal antibodies towards Staphylococcus spp. and Propionibacterium acnes were applied for further species identification. Inflamed follicles were associated with bacterial colonization in 10 samples (26%) and fungal colonization in three samples (8%). Staphylococcus spp. were observed in inflamed follicles in seven samples (18%). Two samples were positive for P. acnes, which were identified as either type II or type IB/type III. Both Staphylococcus spp. and P. acnes were seen in macrocolonies/biofilm structures. In conclusion, one-third of patients with clinically diagnosed, non-infectious folliculitis exhibited microbial colonization with predominance of Staphylococcus spp.

  • 21.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlberg, Ida
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Tamayo, Natalia Curiche
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Mcdowell, Andrew
    Patrick, Sheila
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    No link between rosacea and Propionibacterium acnes2012In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 120, no 11, p. 922-925Article in journal (Refereed)
    Abstract [en]

    Rosacea is a common skin disease in adults affecting mainly the facial skin. Although inflammation appears to play a pathogenic role in rosacea, initiating factors are largely unknown. Microbial involvement in the development of rosacea has been suggested previously. We aimed to visualize Propionibacterium acnes in the skin compartments of rosacea patients. Facial skin biopsies from 82 rosacea patients and 25 controls were stained with a P. acnes-specific monoclonal antibody (QUBPa3). Seven of 82 patients (8.5%) tested positive for P. acnes which was present either as a biofilm (57% of positive) or a microcolony (43%) in colonized patients. Our results suggest that P. acnes does not play a major role in the pathogenesis of rosacea.

  • 22.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, R
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Palmer, Ruth H
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Zouboulis, C C
    McDowell, A
    Patrick, S
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 167, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Summary Background  Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. Objectives  This case-control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. Methods  Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co-haemolysin CAMP factor, a putative virulence determinant. Results  Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23-9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22-12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. Conclusions  We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.

  • 23.
    Jahns, Anika C.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nosek, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Killasli, H.
    Emtestam, L.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Microbiology of folliculitis decalvans: a histological study of 37 patients2015In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 5, p. 1025-1026Article in journal (Other academic)
  • 24.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Oprica, Cristina
    Karolinska Institute, Södersjukhuset, Stockholm.
    Vassilaki, Ismini
    Karolinska University Hospital, Stockholm.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Palmer, Ruth H
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Simultaneous visualization of Propionibacterium acnes and Propionibacterium granulosum with immunofluorescence and fluorescence in situ hybridization2013In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 23, p. 48-54Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes (P. acnes) and Propionibacterium granulosum (P. granulosum) are common skin colonizers that are implicated as possible contributing factors in acne vulgaris development. We have established direct visualization tools for the simultaneous detection of these closely related species with immunofluorescence assay and fluorescence in situ hybridization (FISH). As proof of principle, we were able to distinguish P. acnes and P. granulosum bacteria in multi-species populations in vitro as well as in a mock skin infection model upon labelling with 16S rRNA probes in combinatorial FISH as well as with antibodies. Furthermore, we report the co-localization of P. acnes and P. granulosum in the stratum corneum and hair follicles from patients with acne vulgaris as well as in healthy individuals. Further studies on the spatial distribution of these bacteria in skin structures in various skin disorders are needed.

  • 25.
    Jahns, Anika
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Killasli, Hassan
    Nosek, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lenngren, Anna
    Muratova, Zhanna
    Emtestam, Lennart
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Microbiology of hidradenitis suppurativa (acne inversa): a histological study of 27 patients2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 9, p. 804-809Article in journal (Refereed)
    Abstract [en]

    Hidradenitis suppurativa (acne inverse) (HS) is a chronic skin disease primarily affecting hair follicles. The aetiology of HS is unknown, but infection is believed to play some role. This retrospective study investigated the microbial colonization directly in skin appendices in HS skin samples. Archival samples from 27 patients with HS were screened by immunofluorescence labelling with monoclonal and polyclonal antibodies against Gram-positive bacteria, Propionibacterium acnes and Propionibacterium granulosum. Fluorescence in situ hybridization was used for further species identification of Staphylococcus spp. Overall, 17 patients (63%) were found positive for bacterial colonization. Of these, 15 showed colonization in hair follicles and/or sinus tracts. The most commonly identified bacteria were DAPI labelled coccoids that were seen in 71% of the positive patients in the form of biofilms and microcolonies. P. acnes was found as biofilms in hair follicles of two patients. Staphylococcus aureus and coagulase-negative staphylococci were not detected in any sample. The results of this study indicate a common bacterial presence in HS skin lesions. Bacterial biofilms are not uncommon and their pathogenic role needs further evaluation.

  • 26.
    Omer, Hélène
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    McDowell, Andrew
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Understanding the role of Propionibacterium acnes in acne vulgaris: The critical importance of skin sampling methodologies2017In: Clinics in Dermatology, ISSN 0738-081X, E-ISSN 1879-1131, Vol. 35, no 2, p. 118-129Article in journal (Refereed)
    Abstract [en]

    Acne vulgaris is a chronic inflammatory skin condition classified by the Global Burden of Disease Study as the eighth most prevalent disease worldwide. The pathophysiology of the condition has been extensively studied, with an increase in sebum production, abnormal keratinization of the pilosebaceous follicle, and an inflammatory immune response all implicated in its etiology. One of the most disputed points, however, is the role of the gram:positive anaerobic bacterium Propionibacterium acnes in the development of acne, particularly when this organism is also found in normal sebaceous follicles of healthy skin. Against this background, we now describe the different sampling strategies that have been adopted for qualitative and quantitative study of P acnes within intact hair follicles of the skin and discuss the strengths and weaknesses of such methodologies for investigating the role of P acnes in the development of acne. 

  • 27.
    Persson, Gabriella
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson-Jänkänpää, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, Ruta
    Karadag, Ayse Serap
    Bilgili, Serap Gunes
    Omer, Hélène
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    No evidence for follicular keratinocyte hyperproliferation in acne lesions as compared to autologous healthy hair follicles2018In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 27, no 6, p. 668-671Article in journal (Refereed)
    Abstract [en]

    Abnormal hyperkeratinization in sebaceous hair follicles has long been believed to play an important role in acne pathogenesis. Several early reports purported to provide histological evidence for hyperproliferation of keratinocytes in acne lesions by showing a higher expression of the Ki67 as well as certain keratins. The evidence is, however, not robust, and a number of methodological and technical limitations can be identified in these studies. In this study, we looked at the expression of proliferation, mitosis and apoptosis markers directly at acne skin lesions in 66 patients with acne vulgaris. Ki67 was assessed using immunohistochemistry and -tubulin, phospho-histone H3 and cleaved-PARP with immunofluorescence microscopy. Allogenic unaffected hair follicles from the same acne patients were used as an internal control. In both acne and control hair follicles, the -tubulin staining was universal, approaching 100% cells and showed no signs of changed assembly. Expression of cleaved-PARPthe apoptosis markerwas a rare event. Cell proliferation rate measured by the expression of Ki67 and phospho-histone H3 was virtually identical between acne and the two control groups. Our findings show the absence of increased keratinocyte proliferation in acne vulgaris. Alternative mechanisms are likely responsible for infundibular hyperkeratinization in acne pathogenesis.

  • 28.
    Witek, Barbara
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    El Wakil, Abeer
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Nord, Christoffer
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Eriksson, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Vernersson-Lindahl, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Helland, Aslaug
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallberg, Bengt
    Palmer, Ruth H.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg.
    Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0123542Article in journal (Refereed)
    Abstract [en]

    Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

  • 29.
    Yanamandra, Kiran
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Alexeyev, Oleg
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zamotin, Vladimir
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Srivastava, Vaibhav
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Shchukarev, Andrey
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Brorsson, Ann-Christin
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Tartaglia, Gian Gaetano
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Vogl, Thomas
    Institute of Immunology, University of Münster, Münster, Germany.
    Kayed, Rakez
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
    Wingsle, Gunnar
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Olsson, Jan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dobson, Christopher M
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 5, p. e5562-Article in journal (Refereed)
    Abstract [en]

    Background The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon - prostate tissue remodelling in middle-aged and elderly men.

    Methodology/Principal Findings By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions.

    Conclusions/Significance These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.

1 - 29 of 29
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