Metagenomic study of the human skin microbiome associated with acne

The human microbiota contributes to our normal postnatal development and plays a significant role in defining our physiology. To understand the role of microbiota in human health and disease, we study the skin microbiome in pilosebaceous units (hair follicles) and its association with acne.

Acne is one of the most common skin diseases. Although its etiology still needs to be defined, a bacterial factor has been suggested in the development of the disease. In fact, antibiotic therapy targeting _Propionibacterium acnes_ has been a mainstay treatment for more than 30 years.

Our preliminary study shows that the microcomedone, a specialized skin compartment where acne arises, has a tractable microbiome, with a single dominant species, _P. acnes_. This system offers a unique advantage allowing in-depth analysis of a human microbiome at the subspecies level by sequencing. Our preliminary study suggests that the microbiome associated with acne offers promise for understanding the correlation between the composition of the microbiome and human health and disease.

The goal of the project is to determine whether the microbiota in the pilosebaceous units contributes to acne. We plan to investigate the microbiome associated with acne in three directions. First, we plan to investigate the strain diversity of _P. acnes_ in a disease cohort and a normal cohort and examine whether certain strains of _P. acnes_ are correlated with the disease. Second, we plan to investigate the non- _P. acnes_ microbes in microcomedones and disease lesions and examine whether they correlate with acne pathogenesis. Third, we will examine the interactions between the microbes and the host by transcriptional profiling of both the microbiota and the host.

During the first year of this project, two main questions were asked. 1. Are certain strains of _P. acnes_ associated with acne, but rarely found in normal individuals? 2. If specific strains are associated with acne, what are the differences in their genetic composition compared to other _P. acnes_ strains that are not associated with acne? We collected microcomedone samples from more than 100 subjects, including acne patients and normal individuals. Genomic DNA was extracted from each sample, and 16S rDNA was amplified using universal primers (8F and 1510R), cloned and sequenced using Sanger method. Approximately 384 near full length 16S rDNA sequences were obtained for each sample. Some of the microcomedone samples were also cultured under anaerobic condition to isolate different P. acnes strains. Sixty-eight isolates were selected for whole genome shotgun sequencing using Solexa/Illumina platform. By the end of the first year of the project, we completed the sequencing of more than 40,000 16S rDNA clones and 68 genomes of _P. acnes_ isolates.
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Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and Antibiotic-Resistant Strain HL411PA1.

Propionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1

A study of the problems associated with Dalangdian reservoir, China

There are over 2,300 lakes over 1 km2 in China (total area 80 000 km2). In addition there are approximately 87 000 reservoirs with a storage capacity of 413 billion m3. These form the main supply of drinking water as well as water for industrial and agricultural production and aquaculture. Because of a lack of understanding of the frailty of lake ecosystems and poor environmental awareness, human activities have greatly affected freshwater systems. This article focuses on the problems of one water supply reservoir, Dalangdian Reservoir, and considers options for improving its management. Dalangdian Reservoir is described and occurrence of algal genera given. The authors conclude with remarks on the future of the Dalangdian Reservoir

An expanded multilocus sequence typing scheme for propionibacterium acnes : investigation of 'pathogenic', 'commensal' and antibiotic resistant strains

The Gram-positive bacterium Propionibacterium acnes is a member of the normal human skin microbiota and is associated with various infections and clinical conditions. There is tentative evidence to suggest that certain lineages may be associated with disease and others with health. We recently described a multilocus sequence typing scheme (MLST) for P. acnes based on seven housekeeping genes (http://pubmlst.org/pacnes). We now describe an expanded eight gene version based on six housekeeping genes and two ‘putative virulence’ genes (eMLST) that provides improved high resolution typing (91eSTs from 285 isolates), and generates phylogenies congruent with those based on whole genome analysis. When compared with the nine gene MLST scheme developed at the University of Bath, UK, and utilised by researchers at Aarhus University, Denmark, the eMLST method offers greater resolution. Using the scheme, we examined 208 isolates from disparate clinical sources, and 77 isolates from healthy skin. Acne was predominately associated with type IA1 clonal complexes CC1, CC3 and CC4; with eST1 and eST3 lineages being highly represented. In contrast, type IA2 strains were recovered at a rate similar to type IB and II organisms. Ophthalmic infections were predominately associated with type IA1 and IA2 strains, while type IB and II were more frequently recovered from soft tissue and retrieved medical devices. Strains with rRNA mutations conferring resistance to antibiotics used in acne treatment were dominated by eST3, with some evidence for intercontinental spread. In contrast, despite its high association with acne, only a small number of resistant CC1 eSTs were identified. A number of eSTs were only recovered from healthy skin, particularly eSTs representing CC72 (type II) and CC77 (type III). Collectively our data lends support to the view that pathogenic versus truly commensal lineages of P. acnes may exist. This is likely to have important therapeutic and diagnostic implications

Informal traders lock horns with the formal milk industry: the role of research in pro-poor dairy policy shift in Kenya

A polarizable atomic multipole-based force field for the membrane bilayer models 1,2-dioleoyl-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) has been developed. The force field adopts the same framework as the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) model, in which the charge distribution of each atom is represented by the permanent atomic monopole, dipole and quadrupole moments. Many-body polarization including the inter- and intra-molecular polarization is modelled in a consistent manner with distributed atomic polarizabilities. The van der Waals parameters were first transferred from existing AMOEBA parameters for small organic molecules and then optimised by fitting to ab initio intermolecular interaction energies between models and a water molecule. Molecular dynamics simulations of the two aqueous DOPC and POPE membrane bilayer systems, consisting of 72 model molecules, were then carried out to validate the force field parameters. Membrane width, area per lipid, volume per lipid, deuterium order parameters, electron density profile, etc. were consistent with experimental values