Propionibacterium acnes CAMP Factor and Host Acid Sphingomyelinase Contribute to Bacterial Virulence: Potential Targets for Inflammatory Acne Treatment

Abstract

BackgroundIn 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.Methodology/Principal FindingsWe 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.Conclusions/SignificanceThese 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.

Immunization against Multidrug-Resistant Acinetobacter baumannii Effectively Protects Mice in both Pneumonia and Sepsis Models

“…There have been many previously published vaccine studies on ICR mice [29]–[32]. ICR mice are outbred mice with genetic functional diversity.…”

Different Propionibacterium acnes Phylotypes Induce Distinct Immune Responses and Express Unique Surface and Secreted Proteomes

“…Vaccination with P. acnes CAMP factor 2 (50842175), found in all phylotypes we examined, showed promise in animal models (Liu et al, 2011;Nakatsuji et al, 2011). Some of the cell surface proteins expressed only in acne or neutral strains such as the cell wall hydrolase (50843410), adhesion (50843565), or others may also be interesting to evaluate as vaccine candidates.…”

Cardiolipin Synthetase Is Involved in Antagonistic Interaction (Reverse CAMP Phenomenon) of Mycoplasma Species with Staphylococcus aureus Beta-Hemolysis

“…Indeed, previous studies have shown an association between the putative CAMP factor and virulence (44,45). Rühlmann et al (46) have shown that the CAMP factor of GBS, a 25-kDa protein named protein B, binds to immunoglobulins in a way similar to that of protein A of S. aureus.…”