RESUMO
BACKGROUND: Cutibacterium (Propionibacterium) acnes is assumed to play an important role in the pathogenesis of acne. OBJECTIVES: To examine if clones with distinct virulence properties are associated with acne. METHODS: Multiple C. acnes isolates from follicles and surface skin of patients with moderate to severe acne and healthy controls were characterized by multilocus sequence typing. To determine if CC18 isolates from acne patients differ from those of controls in the possession of virulence genes or lack of genes conducive to a harmonious coexistence the full genomes of dominating CC18 follicular clones from six patients and five controls were sequenced. RESULTS: Individuals carried one to ten clones simultaneously. The dominating C. acnes clones in follicles from acne patients were exclusively from the phylogenetic clade I-1a and all belonged to clonal complex CC18 with the exception of one patient dominated by the worldwide-disseminated and often antibiotic resistant clone ST3. The clonal composition of healthy follicles showed a more heterogeneous pattern with follicles dominated by clones representing the phylogenetic clades I-1a, I-1b, I-2 and II. Comparison of follicular CC18 gene contents, allelic versions of putative virulence genes and their promoter regions, and 54 variable-length intragenic and inter-genic homopolymeric tracts showed extensive conservation and no difference associated with the clinical origin of isolates. CONCLUSIONS: The study supports that C. acnes strains from clonal complex CC18 and the often antibiotic resistant clone ST3 are associated with acne and suggests that susceptibility of the host rather than differences within these clones may determine the clinical outcome of colonization.
Assuntos
Acne Vulgar/microbiologia , Variação Genética , Infecções por Bactérias Gram-Positivas/microbiologia , Voluntários Saudáveis , Propionibacterium acnes/classificação , Propionibacterium acnes/isolamento & purificação , Adolescente , Adulto , Feminino , Genótipo , Humanos , Masculino , Tipagem de Sequências Multilocus , Propionibacterium acnes/genética , Pele/microbiologia , Fatores de Virulência/análise , Fatores de Virulência/genética , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
Current clinical and microbiological information on acne fails to demonstrate a clear association between particular species, including Propionibacterium acnes, and disease, and the disease continues to be a considerable problem. To test if acne is associated with hitherto uncultured bacteria residing in diseased skin follicles, sequencing and phylogenetic analysis of approximately 5,700 amplified and cloned 16S rRNA genes were used to determine the microbial diversity in follicles from acne patients and healthy individuals and from the superficial skin of acne patients. Follicles from healthy skin were exclusively colonized by P. acnes, whereas the follicular microbiota of acne patients included, in addition, Staphylococcus epidermidis and minor proportions of other species. In comparison, samples from superficial skin showed a complex microbiota represented by 12 to 16 bacterial species. The findings of the study exclude the possibility that acne is associated with yet-uncultured bacteria and shows that healthy skin follicles constitute a remarkably exclusive habitat allowing colonization only by P. acnes.
Assuntos
Acne Vulgar/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Biodiversidade , Adolescente , Adulto , Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Genes de RNAr , Folículo Piloso/microbiologia , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Pele/microbiologiaRESUMO
Recent data suggest clinical efficacy of specific antigens delivered at mucosal sites in the treatment of certain organ specific autoimmune diseases. This approach appears non-toxic and has no side effects. Phase I/II human trials on multiple sclerosis and rheumatoid arthritis show positive outcomes. Furthermore, animal studies point to beneficial effects on uveitis, diabetes mellitus, transplantation reactions and allergic diseases. The immunological mechanism is oral tolerance, a well known principle for induction of a systemic hyporesponse to specific antigens. The tolerance is most pronounced on delayed type hypersensibility and IgE-mediated reactions. At least three different mechanisms mediate the tolerance. Low doses of antigen induce active suppression, intermediate doses induce clonal T-cell anergy, and high doses induce clonal T-cell deletion. The recent improvements in the understanding of the mechanisms of oral tolerance have fueled an interest in manipulating this principle to develop anti-inflammatory vaccines.
