Characterization of Propionibacterium acnes isolates from sarcoid and non-sarcoid tissues with special reference to cell invasiveness, serotype, and trigger factor gene polymorphism Asuka Furukawa a , Keisuke Uchida a , Yuki Ishige a , Ikuo Ishige b , Intetsu Kobayashi c , Tamiko Takemura d , Tetsuji Yokoyama e , Kazuo Iwai f , Kunitomo Watanabe g , Shinichiro Shimizu h , Noriko Ishida a , Yoshimi Suzuki a , Takashige Suzuki a , Tetsuo Yamada a , Takashi Ito a , Yoshinobu Eishi a, * a Department of Human Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan b Laboratory of Stem Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan c Chemotherapy Division, Mitsubishi Kagaku Bio-Clinical Laboratory, Tokyo, Japan d Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan e Department of Technology Assessment and Biostatistics, National Institute of Public Health, Saitama, Japan f Division of Molecular Pathology, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan g Division of Anaerobe Research, Life Science Research Center, Gifu University, Gifu, Japan h Department of Pathology, Funabashi Municipal Medical Center, Chiba, Japan article info Article history: Received 12 February 2008 Received in revised form 22 October 2008 Accepted 31 October 2008 Available online 17 November 2008 Keywords: Propionibacterium acnes Sarcoidosis Cell invasiveness Serotype Trigger factor abstract Sarcoidosis is a systemic granulomatous disease of unknown etiology. Propionibacterium acnes is the only microorganism so far isolated from sarcoid lesions. To examine whether P. acnes isolates from sarcoid tissues differ from those obtained from non-sarcoid tissues, we studied cell invasiveness, serotype, and polymorphisms of the P. acnes trigger factor protein and the two invasion-associated proteins (named PAmce and PAp60) in 35 P. acnes isolates from sarcoid lymph nodes and 127 isolates from non-sarcoid tissues. Most of the serotype I isolates (79/112; 71%), but none of the serotype II isolates (0/50) were cell- invasive. Two prominent types of trigger factors, one with and one without a 15 amino acid-residue deletion, corresponded to serotype II and serotype I, respectively. Non-invasive isolates had genomic mutations that caused more than one amino acid change in either the PAmce or PAp60 gene, with four exceptional isolates. P. acnes was finally classified into nine isotypes, and isolates obtained from sarcoid and non-sarcoid tissue did not differ. Although the finding did not link P. acnes to sarcoidosis, the present study clarified the cell invasiveness of P. acnes and the close correlation of cell invasiveness to the serotype and genotype of the two invasion-associated P. acnes genes. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Propionibacterium acnes is a Gram-positive, non-spore-forming, anaerobic bacillus, found predominantly in the sebaceous gland- rich areas of the skin in adults [1]. It can also be isolated from the conjunctiva, external ear canal, mouth, upper respiratory tract, and intestine [2]. Historically, P. acnes has been thought to be of low virulence but was recently found to be the causative agent in various pathologies. P. acnes is most notably implicated in acne vulgaris [3], but it is also associated with endophthalmitis [4], endocarditis [5], osteomyelitis [6], prosthetic hip infection [7], severe sciatica [8], and prostatic inflammation [9]. Sarcoidosis, a systemic granulomatous disease of unknown etiology, seems to result from an antigen-driven immune response of a genetically predisposed subject to an environmental agent, possibly an infec- tious agent [10]. P. acnes is the only microorganism that has been isolated from sarcoid lesions [11]. Many P. acnes genomes have been detected in sarcoid lymph nodes using quantitative PCR [12,13] and in sarcoid granulomas by in situ hybridization [14], thus suggesting an etiologic link between P. acnes and some cases of sarcoidosis. Evaluation of the possible connection of P. acnes to the etiology of sarcoidosis is difficult because the bacterium has been cultured from the lungs and mediastinal lymph nodes of some patients with diseases other than sarcoidosis serving as controls [11], and a few P. acnes cells have been detected in some superficial, gastric, and mediastinal lymph nodes of other such patients [12,13]. P. acnes might also cause latent infection in peripheral lung tissue and mediastinal lymph nodes [15]. As these organs are frequently involved in sarcoidosis, local proliferation of P. acnes at the sites of * Corresponding author. Department of Human Pathology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bnkyo-ku, Tokyo 113-8510, Japan. Tel.: þ81 3 5803 5964; fax: þ81 3 5803 0123. E-mail address: eishi.path@tmd.ac.jp (Y. Eishi). Contents lists available at ScienceDirect Microbial Pathogenesis journal homepage: www.elsevier.com/locate/micpath 0882-4010/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.micpath.2008.10.013 Microbial Pathogenesis 46 (2009) 80–87