Different Propionibacterium acnes Phylotypes Induce Distinct Immune Responses and Express Unique Surface and Secreted Proteomes.
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SUBMITTER: Yu Y
PROVIDER: S-EPMC8295477 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Propionibacterium acnes , plays an important role in acne vulgaris and other diseases. However, understanding of the exact mechanisms of P. acnes pathogenesis is limited. Few studies have investigated its proteome, which is essential for vaccine development. Here, we comprehensively investigate the proteome of P. acnes strain ATCC 6919, including secreted, cell wall, membrane, and cytosolic fractions in three types of growth media. A total of 531 proteins were quantified using an Orbitrap mass spectrometer and bioinformatically categorized for localization and function. Several, including PPA1939, a highly expressed surface and secreted protein, were identified as potential vaccine candidates.
| S-EPMC5224034 | biostudies-literature
Project description:BackgroundThe anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles; however, it also exhibits many traits of an opportunistic pathogen, playing roles in a variety of inflammatory diseases such as acne vulgaris. To date, the underlying disease-causing mechanisms remain ill-defined and knowledge of P. acnes virulence factors remains scarce. Here, we identified proteins secreted during anaerobic cultivation of a range of skin and clinical P. acnes isolates, spanning the four known phylogenetic groups.ResultsCulture supernatant proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE) and all Coomassie-stained spots were subsequently identified by MALDI mass spectrometry (MALDI-MS). A set of 20 proteins was secreted in the mid-exponential growth phase by the majority of strains tested. Functional annotation revealed that many of these common proteins possess degrading activities, including glycoside hydrolases with similarities to endoglycoceramidase, β-N-acetylglucosaminidase and muramidase; esterases such as lysophospholipase and triacylglycerol lipase; and several proteases. Other secreted factors included Christie-Atkins-Munch-Petersen (CAMP) factors, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and several hypothetical proteins, a few of which are unique to P. acnes. Strain-specific differences were apparent, mostly in the secretion of putative adhesins, whose genes exhibit variable phase variation-like sequence signatures.ConclusionsOur proteomic investigations have revealed that the P. acnes secretome harbors several proteins likely to play a role in host-tissue degradation and inflammation. Despite a large overlap between the secretomes of all four P. acnes phylotypes, distinct differences between predicted host-tissue interacting proteins were identified, providing potential insight into the differential virulence properties of P. acnes isolates. Thus, our data presents a rich resource for guiding much-needed investigations on P. acnes virulence factors and host interacting properties.
| S-EPMC3224659 | biostudies-literature
Project description:Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported. Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P. acnes isolates. Analysis of isolates from failed prosthetic hip implants (n = 40) revealed approximately equal numbers of type I and II organisms. Isolates from failed prosthetic hip-associated bone (n = 6) and tissue (n = 38) samples, as well as isolates from acne (n = 22), dental infections (n = 8), and skin removed during surgical incision (n = 18) were predominately of type I. A total of 11 (8%) isolates showed atypical MAb labeling and could not be conclusively identified. Phylogenetic analysis of P. acnes by nucleotide sequencing revealed the 16S rRNA gene to be highly conserved between types I and II. In contrast, sequence analysis of recA and a putative hemolysin gene (tly) revealed significantly greater type-specific polymorphisms that corresponded to phylogenetically distinct cluster groups. All 11 isolates with atypical MAb labeling were identified as type I by sequencing. Within the recA and tly phylogenetic trees, nine of these isolates formed a cluster distinct from other type I organisms, suggesting a further phylogenetic subdivision within type I. Our study therefore demonstrates that the phenotypic differences between P. acnes types I and II reflect deeper differences in their phylogeny. Furthermore, nucleotide sequencing provides an accurate method for identifying the type status of P. acnes isolates.
| S-EPMC540145 | biostudies-literature
Project description:Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp. nov., with strains from the type I and II divisions collectively classified as P. acnessubsp. acnes subsp. nov. Under such a taxonomic re-appraisal, we believe that types I and II should also have their own separate rank of subspecies. In support of this, we describe a polyphasic taxonomic study based on the analysis of publicly available multilocus and whole-genome sequence datasets, alongside a systematic review of previously published phylogenetic, genomic, phenotypic and clinical data. Strains of types I and II form highly distinct clades on the basis of multilocus sequence analysis (MLSA) and whole-genome phylogenetic reconstructions. In silico or digital DNA-DNA similarity values also fall within the 70-80 % boundary recommended for bacterial subspecies. Furthermore, we see important differences in genome content, including the presence of an active CRISPR/Cas system in type II strains, but not type I, and evidence for increasing linkage equilibrium within the separate divisions. Key biochemical differences include positive test results for β-haemolytic, neuraminidase and sorbitol fermentation activities with type I strains, but not type II. We now propose that type I strains should be classified as P. acnessubsp. acnes subsp. nov., and type II as P. acnessubsp. defendens subsp. nov. The type strain of P. acnessubsp. acnes subsp. nov. is NCTC 737T (=ATCC 6919T=JCM 6425T=DSM 1897T=CCUG 1794T), while the type strain of P. acnessubsp. defendens subsp. nov. is ATCC 11828 (=JCM 6473=CCUG 6369).
| S-EPMC6978983 | biostudies-literature
Project description:Viruses specifically infecting bacteria, or bacteriophages, are the most common biological entity in the biosphere. As such, they greatly influence bacteria, both in terms of enhancing their virulence and in terms of killing them. Since the first identification of bacteriophages in the beginning of the 20th century, researchers have been fascinated by these microorganisms and their ability to eradicate bacteria. In this review, we will cover the history of the Propionibacterium acnes bacteriophage research and point out how bacteriophage research has been an important part of the research on P. acnes itself. We will further discuss recent findings from phage genome sequencing and the identification of phage sequence signatures in clustered regularly interspaced short palindromic repeats (CRISPRs). Finally, the potential to use P. acnes bacteriophages as a therapeutic strategy to combat P. acnes-associated diseases will be discussed.
| S-EPMC3652107 | biostudies-literature
Project description:Propionibacterium acnes (P. acnes) is a major skin-associated bacterium that was long considered commensal, until several studies revealed it to be an opportunistic pathogen. We investigated the ability of P. acnes surface proteins to recognize ECM proteins and showed that a 58 kDa P. acnes surface protein was specifically recognized by human fibrinogen (hFg). The 58 kDa protein was further characterized by two-dimensional (2-D) electrophoresis and MALDI-ToF as a P. acnes host cell-surface attachment protein, PA25957, recognizing dermatan sulfate (DsA1). This protein sequence contains 432 amino acids with the presence of three structurally different domains: an N-terminal signal peptide, a C-terminal LPXTG motif, and a PT repeat region. DsA1 is mostly produced during stationary phase. It appears to be highly glycosylated, containing GalNAc residues. Purified DsA1 strongly recognizes the Aα and Bβ subunits of hFg, and specific enzymatic deglycosylation of hFg demonstrated the involvement of the protein backbone in the recognition process. The Bβ subunit of hFg was cloned in four peptide fractions (Fg1-Fg4). The N-terminal Fg1 peptide of hFg was recognized by DsA1, and priming DsA1 with Fg1 inhibited DsA1/hFg recognition. We describe here for the first time, the characterization of a P. acnes surface glycoprotein recognizing human fibrinogen.
| S-EPMC5527093 | biostudies-literature
Project description:Hyaluronic acid (HA) and other glycosaminoglycans are extracellular matrix components in the human epidermis and dermis. One of the most prevalent skin microorganisms, Propionibacterium acnes, possesses HA-degrading activity, possibly conferred by the enzyme hyaluronate lyase (HYL). In this study, we identified the HYL of P. acnes and investigated the genotypic and phenotypic characteristics. Investigations include the generation of a P. acneshyl knockout mutant and HYL activity assays to determine the substrate range and formed products. We found that P. acnes employs two distinct variants of HYL. One variant, HYL-IB/II, is highly active, resulting in complete HA degradation; it is present in strains of the phylotypes IB and II. The other variant, HYL-IA, has low activity, resulting in incomplete HA degradation; it is present in type IA strains. Our findings could explain some of the observed differences between P. acnes phylotype IA and IB/II strains. Whereas type IA strains are primarily found on the skin surface and associated with acne vulgaris, type IB/II strains are more often associated with soft and deep tissue infections, which would require elaborate tissue invasion strategies, possibly accomplished by a highly active HYL-IB/II.
| S-EPMC5620648 | biostudies-literature
Project description:Propionibacterium acnes (P. acnes) bacteria play a key role in the pathogenesis of acne vulgaris. Although our previous studies have demonstrated that vaccines targeting a surface sialidase or bacterial particles exhibit a preventive effect against P. acnes, the lack of therapeutic activities and incapability of neutralizing secretory virulence factors motivate us to generate novel immunotherapeutics. In this study, we develop an immunotherapeutic antibody to secretory Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes. Via agroinfiltration, P. acnes CAMP factor was encapsulated into the leaves of radishes. ICR mice intranasally immunized with whole leaves expressing CAMP factor successfully produced neutralizing antibodies that efficiently attenuated P. acnes-induced ear swelling and production of macrophage-inflammatory protein-2. Passive neutralization of CAMP factor enhanced immunity to eradicate P. acnes at the infection site without influencing bacterial growth elsewhere. We propose that CAMP factor is a novel therapeutic target for the treatment of various P. acnes-associated diseases and highlight the concept of neutralizing P. acnes virulence without disturbing the bacterial commensalism in human microbiome.
| S-EPMC3388602 | biostudies-literature
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.
| S-EPMC3124536 | biostudies-literature
Project description:ObjectivesTo study the characteristics of patients with Propionibacterium acnes prosthetic valve endocarditis (PVE) who required surgery.MethodsA single-centre retrospective cohort study was conducted during a 7-year period. Patients with definite infective P. acnes endocarditis, according to the modified Duke criteria, were included. An extended culture protocol was applied. Information on medical health status, surgery, antibiotic treatment and mortality was obtained.ResultsThirteen patients fulfilled the criteria for P. acnes endocarditis (0.53% of 2466 patients with valve replacement in a 7-year period). All patients were male and had a previous valve replacement. The health status of patients was poor at diagnosis of P. acnes PVE. Most patients (11 of 13, 85%) were admitted with signs of heart failure due to a significant paravalvular leak; 2 of 13 (15%) patients presented with septic emboli. Twelve patients needed redo surgery, whereas one could be treated with antibiotic therapy only. The time between the index surgery and presentation with P. acnes PVE varied between 5 and 135 months (median 26.5 months). Replacement and reconstruction of the dysfunctional valve and affected anatomical structures was mainly performed with a mechanical valve (n = 5, 42%) or a (bio-) Bentall prosthesis (n = 6, 50%). Antibiotic therapy consisted of penicillin with or without rifampicin for 6 weeks after surgery. The mortality in this series was low (n = 1, 8%) and no recurrent endocarditis was found during a median follow-up of 38 months.ConclusionsPropionibacterium acnes PVE is a rare complication after valve surgery. Redo surgery is often required. Treatment of the dysfunctional prosthetic aortic valve most often consists of root replacement, in combination with antibiotic therapy.
| S-EPMC4986751 | biostudies-literature