Abstract

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.

Highlights

  • The Gram-positive bacterium Propionibacterium acnes is considered as a skin commensal, which preferentially resides in sebaceous follicles

  • This assumption has been bolstered by immunological observations in vitro, demonstrating that P. acnes possesses extensive immunostimulatory activity that triggers the secretion of proinflammatory cytokines and chemokines, the activation of the complement system and the stimulation of T-cells [5,6,7,8]

  • P. acnes strains belonging to different phylotypes are reported to differ in their immunostimulatory activity; for instance, strains vary in their ability to trigger human-beta-defensin 2 in keratinocytes, and in their effect on differentiation and viability of sebocytes [9,10,11,12]

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Summary

Introduction

The Gram-positive bacterium Propionibacterium acnes is considered as a skin commensal, which preferentially resides in sebaceous follicles. The bacterium’s presence was considered as contamination or secondary invasion; more recently, there is growing awareness that P. acnes could be an etiological agent of at least some of these diseases [4]. This assumption has been bolstered by immunological observations in vitro, demonstrating that P. acnes possesses extensive immunostimulatory activity that triggers the secretion of proinflammatory cytokines and chemokines, the activation of the complement system and the stimulation of T-cells [5,6,7,8]. Bacterial traits and factors responsible for triggering and modulating host cell responses have not been uncovered

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