The involvement of Propionibacterium acnes in the pathogenesis of acne is controversial, mainly owing to its dominance as an inhabitant of healthy skin. This study tested the hypothesis that specific evolutionary lineages of the species are associated with acne while others are compatible with health. Phylogenetic reconstruction based on nine housekeeping genes was performed on 210 isolates of P. acnes from well-characterized patients with acne, various opportunistic infections, and from healthy carriers. Although evidence of recombination was observed, the results showed a basically clonal population structure correlated with allelic variation in the virulence genes tly and camp5, with pulsed field gel electrophoresis (PFGE)- and biotype, and with expressed putative virulence factors. An unexpected geographically and temporal widespread dissemination of some clones was demonstrated. The population comprised three major divisions, one of which, including an epidemic clone, was strongly associated with moderate to severe acne while others were associated with health and opportunistic infections. This dichotomy correlated with previously observed differences in in vitro inflammation-inducing properties. Comparison of five genomes representing acne- and health-associated clones revealed multiple both cluster- and strain-specific genes that suggest major differences in ecological preferences and redefines the spectrum of disease-associated virulence factors. The results of the study indicate that particular clones of P. acnes play an etiologic role in acne while others are associated with health.

Corporate partners of the EDF have been asked to contribute towards this work. GlaxoSmithKline plc. (GSK) and Meda AB have contributed funding for the development of the European evidence-based (S3) guideline for the treatment of acne (update 2016) through an educational grant to the EDF. Sponsors had no influence on the content of the guideline. Support was given independent of any influence on methods or results. Sponsors did not receive any information about methods, group members or likely results. The sources of the funding were not known to the experts of the guideline and were not disclosed before the finalization of the guideline. This is a short summary of the complete version of the S3 European Acne guideline, please see online appendix for full text (Document S1. Long Version) and detailed methods report (DOI: 10.1111/jdv.13783). Expiry date: 31 December 2020 MethodsIn order to weight the different recommendations, the group assigned a 'strength of recommendation'. It considered all aspects of the treatment decision, such as efficacy, safety, patient preference and the reliability of the existing body of evidence. Strength of recommendationIn order to grade the recommendation a "standardized guideline" language was used:

IgA1 protease activity, which allows bacteria to cleave human IgA1 in the hinge region, represents a striking example of convergent evolution of a specific property in bacteria. Although it has been known since 1979 that IgA1 protease is produced by the three leading causes of bacterial meningitis in addition to important urogenital pathogens and some members of the oropharyngeal flora, the exact role of this enzyme in bacterial pathogenesis is still incompletely understood owing to lack of a satisfactory animal model. Cleavage of IgA1 by these post‐proline endopeptidases efficiently separates the monomeric antigen‐binding fragments from the secondary effector functions of the IgA1 antibody molecule. Several in vivo and in vitro observations indicate that the enzymes are important for the ability of bacteria to colonize mucosal membranes in the presence of S‐IgA antibodies. Furthermore, the extensive cleavage of IgA sometimes observed in vivo, suggests that IgA1 protease activity results in a local functional IgA deficiency that may facilitate colonization of other microorganisms and the penetration of potential allergens. It has been hypothesized that IgA1 protease activity of Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, under special immunological circumstances, allows these bacteria to take advantage of specific IgA1 antibodies in a strategy to evade other immune factors of the human body. The decisive factor is the balance between IgA antibodies against surface antigens of the respective bacteria and their IgA1 protease. Recent studies have shown that serine‐type IgA1 proteases of H. influenzae, meningococci, and gonococci belong to a family of proteins used by a diverse group of Gramnegative bacteria for colonization and invasion.

The Gram-positive anaerobic bacterium Propionibacterium acnes is a prevalent member of the normal skin microbiota of human adults. In addition to its suspected role in acne vulgaris it is involved in a variety of opportunistic infections. Multi-locus sequence-typing (MLST) schemes identified distinct phylotypes associated with health and disease. Being based on 8 to 9 house-keeping genes these MLST schemes have a high discriminatory power, but their application is time- and cost-intensive. Here we describe a single-locus sequence typing (SLST) scheme for P. acnes. The target locus was identified with a genome mining approach that took advantage of the availability of representative genome sequences of all known phylotypes of P. acnes. We applied this SLST on a collection of 188 P. acnes strains and demonstrated a resolution comparable to that of existing MLST schemes. Phylogenetic analysis applied to the SLST locus resulted in clustering patterns identical to a reference tree based on core genome sequences. We further demonstrate that SLST can be applied to detect multiple phylotypes in complex microbial communities by a metagenomic pyrosequencing approach. The described SLST strategy may be applied to any bacterial species with a basically clonal population structure to achieve easy typing and mapping of multiple phylotypes in complex microbiotas. The P. acnes SLST database can be found at http://medbac.dk/slst/pacnes.

The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that is occasionally associated with inflammatory diseases. Recent work has indicated that evolutionary distinct lineages of P. acnes play etiologic roles in disease while others are associated with maintenance of skin homeostasis. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis of distinct P. acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a strain. Comparative genome analysis of strain 266 and four other P. acnes strains revealed that overall genome plasticity is relatively low; however, a number of island-like genomic regions, encoding a variety of putative virulence-associated and fitness traits differ between phylotypes, as judged from PCR analysis of a collection of P. acnes strains. Comparative transcriptome analysis of strains KPA171202 (type I-2) and 266 during exponential growth revealed inter-strain differences in gene expression of transport systems and metabolic pathways. In addition, transcript levels of genes encoding possible virulence factors such as dermatan-sulphate adhesin, polyunsaturated fatty acid isomerase, iron acquisition protein HtaA and lipase GehA were upregulated in strain 266. We investigated differential gene expression during exponential and stationary growth phases. Genes encoding components of the energy-conserving respiratory chain as well as secreted and virulence-associated factors were transcribed during the exponential phase, while the stationary growth phase was characterized by upregulation of genes involved in stress responses and amino acid metabolism. Our data highlight the genomic basis for strain diversity and identify, for the first time, the actively transcribed part of the genome, underlining the important role growth status plays in the inflammation-inducing activity of P. acnes. We argue that the disease-causing potential of different P. acnes strains is not only determined by the phylotype-specific genome content but also by variable gene expression.

BackgroundPropionibacterium acnes and Staphylococcus epidermidis live in close proximity on human skin, and both bacterial species can be isolated from normal and acne vulgaris-affected skin sites. The antagonistic interactions between the two species are poorly understood, as well as the potential significance of bacterial interferences for the skin microbiota. Here, we performed simultaneous antagonism assays to detect inhibitory activities between multiple isolates of the two species. Selected strains were sequenced to identify the genomic basis of their antimicrobial phenotypes.ResultsFirst, we screened 77 P. acnes strains isolated from healthy and acne-affected skin, and representing all known phylogenetic clades (I, II, and III), for their antimicrobial activities against 12 S. epidermidis isolates. One particular phylogroup (I-2) exhibited a higher antimicrobial activity than other P. acnes phylogroups. All genomes of type I-2 strains carry an island encoding the biosynthesis of a thiopeptide with possible antimicrobial activity against S. epidermidis.Second, 20 S. epidermidis isolates were examined for inhibitory activity against 25 P. acnes strains. The majority of S. epidermidis strains were able to inhibit P. acnes. Genomes of S. epidermidis strains with strong, medium and no inhibitory activities against P. acnes were sequenced. Genome comparison underlined the diversity of S. epidermidis and detected multiple clade- or strain-specific mobile genetic elements encoding a variety of functions important in antibiotic and stress resistance, biofilm formation and interbacterial competition, including bacteriocins such as epidermin. One isolate with an extraordinary antimicrobial activity against P. acnes harbors a functional ESAT-6 secretion system that might be involved in the antimicrobial activity against P. acnes via the secretion of polymorphic toxins.ConclusionsTaken together, our study suggests that interspecies interactions could potentially jeopardize balances in the skin microbiota. In particular, S. epidermidis strains possess an arsenal of different mechanisms to inhibit P. acnes. However, if such interactions are relevant in skin disorders such as acne vulgaris remains questionable, since no difference in the antimicrobial activity against, or the sensitivity towards S. epidermidis could be detected between health- and acne-associated strains of P. acnes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2489-5) contains supplementary material, which is available to authorized users.

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.

Propionibacterium acnes is a commensal of human skin but is also implicated in the pathogenesis of acne vulgaris, in biofilmassociated infections of medical devices and endophthalmitis, and in infections of bone and dental root canals. Recent studies associate P. acnes with prostate cancer. As the species includes evolutionary lineages with distinct association with health and disease, there is a need for a high-resolution typing scheme. Recently, two multilocus sequence typing (MLST) schemes were reported, one based on nine and one based on seven housekeeping genes. In the present study, the two schemes were compared with reference to a phylogenetic tree based on 78 P. acnes genomes and their gene contents. Further support for a basically clonal population structure of P. acnes and a scenario of the global spread of epidemic clones of P. acnes was obtained. Compared to the Belfast scheme, the Aarhus MLST scheme (http://pacnes.mlst.net/), which is based on nine genes, offers significantly enhanced resolution and phylogenetic inferences more concordant with analyses based on a comprehensive sampling of the entire genomes, their gene contents, and their putative pathogenic potential.