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Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes.

ABSTRACT: BACKGROUND: Propionibacterium acnes is a commensal of human skin but is also known to be involved in certain diseases, such as acne vulgaris and infections of orthopaedic implants. Treatment of these conditions is complicated by increased resistance to antibiotics and/or biofilm formation of P. acnes bacteria. P. acnes can be infected by bacteriophages, but until recently little has been known about these viruses. The aim of this study was to identify and characterize inducible phages from P. acnes on a genetic and morphological basis. RESULTS: More than 70% (65/92) of P. acnes isolates investigated have inducible phages, classified morphologically as Siphoviruses. The phages have a head of 55 nm in diameter and a tail of 145-155 nm in length and 9-10 nm in width. There was no difference in carriage rate of phages between P. acnes isolates from deep infections and isolates from skin. However, there was a significant lower carriage rate of phages in P. acnes biotype IB, mostly attributed to the low carriage rate of inducible phages in biotype IB isolated from deep tissue. Most phages have a strong lytic activity against all P. acnes isolates with inducible phages, but have less lytic activity against isolates that have no prophages. Phages only infected and lysed P. acnes and not other closely related propionibacteria. All phages could infect and lyse their non-induced parental host, indicating that these prophages do not confer superinfection immunity. The phages have identical protein pattern as observed on SDS-PAGE. Finally, sequencing of two phage genes encoding a putative major head protein and an amidase and showed that the phages could be divided into different groups on a genetic basis. CONCLUSION: Our findings indicate that temperate phages are common in P. acnes, and that they are a genetically and functionally homogeneous group of Siphoviruses. The phages are specific for P. acnes and do not seem to confer superinfection immunity.

SUBMITTER: Lood R

PROVIDER: S-EPMC2533672 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes.

Lood Rolf R Mörgelin Matthias M Holmberg Anna A Rasmussen Magnus M Collin Mattias M

BMC microbiology 20080815

<h4>Background</h4>Propionibacterium acnes is a commensal of human skin but is also known to be involved in certain diseases, such as acne vulgaris and infections of orthopaedic implants. Treatment of these conditions is complicated by increased resistance to antibiotics and/or biofilm formation of P. acnes bacteria. P. acnes can be infected by bacteriophages, but until recently little has been known about these viruses. The aim of this study was to identify and characterize inducible phages fro ...[more]

PMID: 18702830

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Project description:Investigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne. Propionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne.

Project description: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.

Project description:Cutibacterium acnes, formerly known as Propionibacterium acnes, is a commensal of the human pilosebaceous unit but also causes deep-seated infection, especially in the context of orthopedic and neurosurgical foreign materials. Interestingly, little is known about the role of specific pathogenicity factors for infection establishment. Here, 86 infection-associated and 103 commensalism-associated isolates of C. acnes were collected from three independent microbiology laboratories. We sequenced the whole genomes of the isolates for genotyping and a genome-wide association study (GWAS). We found that C. acnes subsp. acnes IA1 was the most significant phylotype among the infection isolates (48.3% of all infection isolates; odds ratio [OR] = 1.98 for infection). Among the commensal isolates, C. acnes subsp. acnes IB was the most significant phylotype (40.8% of all commensal isolates; OR = 0.5 for infection). Interestingly, C. acnes subsp. elongatum (III) was rare overall and did not occur at all in infection. The open reading frame-based GWAS (ORF-GWAS) did not show any loci with a strong signal for infection association (no P values of ≤0.05 after adjustment for multiple testing; no logarithmic OR [logOR] of ≥|2|). We concluded that all subspecies and phylotypes of C. acnes, possibly with the exception of C. acnes subsp. elongatum, are able to cause deep-seated infection given favorable conditions, most importantly related to inserted foreign material. Genetic content appears to have a small effect on the likelihood of infection establishment, and functional studies are needed to understand the individual factors contributing to deep-seated infections caused by C. acnes. IMPORTANCE Opportunistic infections emerging from human skin microbiota are of ever-increasing importance. Cutibacterium acnes, being abundant on the human skin, may cause deep-seated infections (e.g., device-associated infections). Differentiation between invasive (i.e., clinically significant) C. acnes isolates and sole contaminants is often difficult. Identification of genetic markers associated with invasiveness not only would strengthen our knowledge related to pathogenesis but also could open ways to selectively categorize invasive and contaminating isolates in the clinical microbiology lab. We show that in contrast to other opportunistic pathogens (e.g., Staphylococcus epidermidis), invasiveness is apparently a broadly distributed ability across almost all C. acnes subspecies and phylotypes. Thus, our work strongly supports an approach in which clinical significance is judged from clinical context rather than by detecting specific genetic traits.

Project description:BackgroundSarcoidosis is caused by Th1-type immune responses to unknown agents, and is linked to the infectious agent Propionibacterium acnes. Many strains of P. acnes isolated from sarcoid lesions cause intracellular infection and autophagy may contribute to the pathogenesis of sarcoidosis. We examined whether P. acnes induces autophagy.MethodsThree cell lines from macrophages (Raw264.7), mesenchymal cells (MEF), and epithelial cells (HeLa) were infected by viable or heat-killed P. acnes (clinical isolate from sarcoid lymph node) at a multiplicity of infection (MOI) of 100 or 1000 for 1 h. Extracellular bacteria were killed by washing and culturing infected cells with antibiotics. Samples were examined by colony assay, electron-microscopy, and fluorescence-microscopy with anti-LC3 and anti-LAMP1 antibodies. Autophagy-deficient (Atg5-/-) MEF cells were also used.ResultsSmall and large (?5 ?m in diameter) LC3-positive vacuoles containing few or many P. acnes cells (LC3-positive P. acnes) were frequently found in the three cell lines when infected by viable P. acnes at MOI 1000. LC3-positive large vacuoles were mostly LAMP1-positive. A few small LC3-positive/LAMP1-negative vacuoles were consistently observed in some infected cells for 24 h postinfection. The number of LC3-positive P. acnes was decreased at MOI 100 and completely abolished when heat-killed P. acnes was used. LC3-positive P. acnes was not found in autophagy-deficient Atg5-/- cells where the rate of infection was 25.3 and 17.6 times greater than that in wild-type Atg5+/+ cells at 48 h postinfection at MOI 100 and 1000, respectively. Electron-microscopic examination revealed bacterial cells surrounded mostly by a single-membrane including the large vacuoles and sometimes a double or multi-layered membrane, with occasional undigested bacterial cells in ruptured late endosomes or in the cytoplasm.ConclusionAutophagy was induced by intracellular P. acnes infection and contributed to intracellular bacterial killing as an additional host defense mechanism to endocytosis or phagocytosis.

Dataset Information

Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes.

Publications

Inducible Siphoviruses in superficial and deep tissue isolates of Propionibacterium acnes.

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