The human skin microbiome plays important roles in skin health and
disease. However, bacterial population structure and diversity at the strain
level is poorly understood. We compared the skin microbiome at the strain level
and genome level of Propionibacterium acnes, a dominant skin
commensal, between 49 acne patients and 52 healthy individuals by sampling the
pilosebaceous units on their noses. Metagenomic analysis demonstrated that while
the relative abundances of P. acnes were similar, the strain
population structures were significantly different in the two cohorts. Certain
strains were highly associated with acne and other strains were enriched in
healthy skin. By sequencing 66 previously unreported P. acnes
strains and comparing 71 P. acnes genomes, we identified
potential genetic determinants of various P. acnes strains in
association with acne or health. Our analysis suggests that acquired DNA
sequences and bacterial immune elements may play roles in determining virulence
properties of P. acnes strains and some could be future targets
for therapeutic interventions. This study demonstrates a previously unreported
paradigm of commensal strain populations that could explain the pathogenesis of
human diseases. It underscores the importance of strain level analysis of the
human microbiome to define the role of commensals in health and disease.
One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-κB activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes. P. acnes also induced activation of IL-12 p40 promoter activity via TLR2. Furthermore, P. acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for treatment of this common skin disease.
Sulfur-rich copolymers based on poly(sulfurrandom-1,3-diisopropenylbenzene) (poly(S-r-DIB)) were synthesized via inverse vulcanization to create cathode materials for lithium−sulfur battery applications. These materials exhibit enhanced capacity retention (1005 mAh/g at 100 cycles) and battery lifetimes over 500 cycles at a C/10 rate. These poly(Sr-DIB) copolymers represent a new class of polymeric electrode materials that exhibit one of the highest charge capacities reported, particularly after extended charge− discharge cycling in Li−S batteries.
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