Resolution of inflammatory acne vulgaris may involve regulation of CD4+ T-cell responses to Propionibacterium acnes

Wilcox, Helen E; Farrar, Mark D.; Cunliffe, W.J.; Holland, K. T.; Ingham, Eileen

doi:10.1111/j.1365-2133.2006.07631.x

Cited by 19 publications

(18 citation statements)

References 26 publications

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“…Heat shock proteins have been implicated in the virulence of P. acnes , for example in the induction of a proinflammatory response in keratinocytes [29], [35]. The genes encoding cytosolic 70-kDa heat-shock protein (Hsp70) chaperones were highly expressed in both growth phases (DnaK, PPA2040; DnaJ, PPA2038; GrpE, PPA2039); the same is true for the trigger factor (PPA1575), a protein with peptidyl-prolyl cis-trans isomerase activity, and the first protein to encounter nascent polypeptide chains as they emerge from the ribosome.…”

Section: Resultsmentioning

confidence: 99%

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Comparative Genomics and Transcriptomics of Propionibacterium acnes

et al. 2011

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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.

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Section: Resultsmentioning

confidence: 99%

“…The RNA levels of these three genes exhibited the strongest growth phase dependency among all genes. GroEL of P. acnes has been implicated in the stimulation of cytokine production, such as interleukin (IL)-1-alpha, tumor necrosis factor (TNF)-alpha or granulocyte/macrophage colony-stimulating factor (GM-CSF) in keratinocytes [35].…”

Section: Resultsmentioning

confidence: 99%

Comparative Genomics and Transcriptomics of Propionibacterium acnes

et al. 2011

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“…90 P. acnes produces several factors, other than its biofilm, which may be of pathogenetic importance. 95 P. acnes can, in some way, activate the complement system and it may stimulate the release of hydrolases from neutrophils. 95 P. acnes can, in some way, activate the complement system and it may stimulate the release of hydrolases from neutrophils.…”

Section: Treatment Of Acne Vulgarismentioning

confidence: 99%

Diseases of cutaneous appendages

Weedon

2010

Weedon's Skin Pathology

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“…P. acnes has been shown to exhibit haemolytic and cytotoxic activities [15,16] as well as extensive immunostimulatory activity and complement activation [6,17-20]. P. acnes isolates differ in their virulence properties, such as in their ability to trigger production of proinflammatory cytokines/chemokines in infected keratinocytes [21,22].…”

Section: Introductionmentioning

confidence: 99%

Proteomic identification of secreted proteins of Propionibacterium acnes

et al. 2010

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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.

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Resolution of inflammatory acne vulgaris may involve regulation of CD4+ T-cell responses to Propionibacterium acnes

Abstract: The significantly lower proportion of resolved donors demonstrating a single-hit kinetics response to P. acnes by LDA may represent negative regulation of the CD4+ T-cell response to P. acnes in these subjects.

Cited by 19 publications

References 26 publications

Comparative Genomics and Transcriptomics of Propionibacterium acnes

Comparative Genomics and Transcriptomics of Propionibacterium acnes

Diseases of cutaneous appendages

Proteomic identification of secreted proteins of Propionibacterium acnes

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