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      Propionibacterium acnes and Acne Vulgaris: New Insights from the Integration of Population Genetic, Multi-Omic, Biochemical and Host-Microbe Studies

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          Abstract

          The anaerobic bacterium Propionibacterium acnes is believed to play an important role in the pathophysiology of the common skin disease acne vulgaris. Over the last 10 years our understanding of the taxonomic and intraspecies diversity of this bacterium has increased tremendously, and with it the realisation that particular strains are associated with skin health while others appear related to disease. This extensive review will cover our current knowledge regarding the association of P. acnes phylogroups, clonal complexes and sequence types with acne vulgaris based on multilocus sequence typing of isolates, and direct ribotyping of the P. acnes strain population in skin microbiome samples based on 16S rDNA metagenomic data. We will also consider how multi-omic and biochemical studies have facilitated our understanding of P. acnes pathogenicity and interactions with the host, thus providing insights into why certain lineages appear to have a heightened capacity to contribute to acne vulgaris development, while others are positively associated with skin health. We conclude with a discussion of new therapeutic strategies that are currently under investigation for acne vulgaris, including vaccination, and consider the potential of these treatments to also perturb beneficial lineages of P. acnes on the skin.

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          Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications

          The PubMLST.org website hosts a collection of open-access, curated databases that integrate population sequence data with provenance and phenotype information for over 100 different microbial species and genera.  Although the PubMLST website was conceived as part of the development of the first multi-locus sequence typing (MLST) scheme in 1998 the software it uses, the Bacterial Isolate Genome Sequence database (BIGSdb, published in 2010), enables PubMLST to include all levels of sequence data, from single gene sequences up to and including complete, finished genomes.  Here we describe developments in the BIGSdb software made from publication to June 2018 and show how the platform realises microbial population genomics for a wide range of applications.  The system is based on the gene-by-gene analysis of microbial genomes, with each deposited sequence annotated and curated to identify the genes present and systematically catalogue their variation.  Originally intended as a means of characterising isolates with typing schemes, the synthesis of sequences and records of genetic variation with provenance and phenotype data permits highly scalable (whole genome sequence data for tens of thousands of isolates) means of addressing a wide range of functional questions, including: the prediction of antimicrobial resistance; likely cross-reactivity with vaccine antigens; and the functional activities of different variants that lead to key phenotypes.  There are no limitations to the number of sequences, genetic loci, allelic variants or schemes (combinations of loci) that can be included, enabling each database to represent an expanding catalogue of the genetic variation of the population in question.  In addition to providing web-accessible analyses and links to third-party analysis and visualisation tools, the BIGSdb software includes a RESTful application programming interface (API) that enables access to all the underlying data for third-party applications and data analysis pipelines.
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            Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis

            Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus , was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium , and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
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              The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions.

              The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                13 May 2019
                May 2019
                : 7
                : 5
                : 128
                Affiliations
                [1 ]Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Londonderry BT47 6SB, UK; McLaughlin-J35@ 123456ulster.ac.uk (J.M.); s.watterson@ 123456ulster.ac.uk (S.W.); aj.bjourson@ 123456ulster.ac.uk (A.J.B.)
                [2 ]Department of Dermatology, Harrogate and District NHS Foundation Trust, Harrogate HG2 7SX, UK; laytona@ 123456btinternet.com
                [3 ]School of Biological Sciences, Queen’s University, Belfast BT9 7AE, UK; e.barnard@ 123456qub.ac.uk
                Author notes
                Author information
                https://orcid.org/0000-0002-9649-0504
                Article
                microorganisms-07-00128
                10.3390/microorganisms7050128
                6560440
                31086023
                9a8f34f1-dd94-46c5-a89d-7fb99b00f991
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 April 2019
                : 09 May 2019
                Categories
                Review

                propionibacterium acnes,cutibacterium,phylogroups,mlst,clonal complex,sequence types,multi-omic analyses,virulence factors,host-microbe interactions,novel therapeutics,vaccination

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