Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment

• Published in: PloS one Vol. 6; no. 4; p. e14797
• Main Authors: Nakatsuji, Teruaki, Tang, De-chu C, Zhang, Liangfang, Gallo, Richard L, Huang, Chun-Ming
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.04.2011; Public Library of Science (PLoS)
• Subjects: Acids; Acne; Acne Vulgaris - drug therapy; Acne Vulgaris - microbiology; Amino acids; Animals; Antiacne agents; Antibiotics; Antibodies; Bacillus anthracis; Bacteria; Bacterial infections; Bacterial Proteins - immunology; Bacterial Proteins - physiology; Biocompatibility; Cell culture; Cell death; Cell growth; Cell Line; Cytotoxicity; Dermatologic Agents - therapeutic use; Dermatology; Dermatology/Acne-Like Disorders; Dermatology/Skin Infections; Desipramine; Desipramine - pharmacology; Disruption; Drug development; Drug therapy; Drugs; E coli; Ear; Humans; Immune system; Immunity; Immunization; Immunosuppressive agents; Infectious Diseases/Skin Infections; Infiltration; Inflammation; Injection; Keratinocytes; Laboratories; Macrophages; Mammals; Mice; Mice, Inbred CBA; Microbiology/Medical Microbiology; Pathogens; Phosphatase; Propionibacterium; Propionibacterium acnes - metabolism; Propionibacterium acnes - pathogenicity; Proteins; Proteomics; Skin; Sphingomyelin phosphodiesterase; Sphingomyelin Phosphodiesterase - antagonists & inhibitors; Sphingomyelin Phosphodiesterase - physiology; Streptococcus agalactiae; Toxicity; Vaccination; Vaccines; Virulence; Virulence (Microbiology); United States > US; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014797

In the progression of acne vulgaris, the disruption of follicular epithelia by an over-growth of Propionibacterium acnes (P. acnes) permits the bacteria to spread and become in contact with various skin and immune cells. We have demonstrated in the present study that the Christie, Atkins, Munch-Peterson (CAMP) factor of P. acnes is a secretory protein with co-hemolytic activity with sphingomyelinase that can confer cytotoxicity to HaCaT keratinocytes and RAW264.7 macrophages. The CAMP factor from bacteria and acid sphingomyelinase (ASMase) from the host cells were simultaneously present in the culture supernatant only when the cells were co-cultured with P. acnes. Either anti-CAMP factor serum or desipramine, a selective ASMase inhibitor, significantly abrogated the P. acnes-induced cell death of HaCaT and RAW264.7 cells. Intradermal injection of ICR mouse ears with live P. acnes induced considerable ear inflammation, macrophage infiltration, and an increase in cellular soluble ASMase. Suppression of ASMase by systemic treatment with desipramine significantly reduced inflammatory reaction induced by intradermal injection with P. acnes, suggesting the contribution of host ASMase in P. acnes-induced inflammatory reaction in vivo. Vaccination of mice with CAMP factor elicited a protective immunity against P. acnes-induced ear inflammation, indicating the involvement of CAMP factor in P. acnes-induced inflammation. Most notably, suppression of both bacterial CAMP factor and host ASMase using vaccination and specific antibody injection, respectively, cooperatively alleviated P. acnes-induced inflammation. These findings envision a novel infectious mechanism by which P. acnes CAMP factor may hijack host ASMase to amplify bacterial virulence to degrade and invade host cells. This work has identified both CAMP factor and ASMase as potential molecular targets for the development of drugs and vaccines against acne vulgaris.