Immunoproteomic Identification ofIn Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model

Abstract

dPropionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implantassociated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes.

Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris

“…Likewise, HK Ca was cross-protective against Actinobacillus pleuropneumoniae in pig and mouse models [ 137 ]. A number of attractive vaccine candidates have been reported from in vivo infection studies, including a rabbit model of implant-associated infection with C. acnes that identified 24 immunogenic proteins upregulated during infection [ 138 ].…”

Clinical and Biological Features of Cutibacterium (Formerly Propionibacterium)avidum, an Underrecognized Microorganism

“…Finally, what about monotherapy treatment and the pharmacokinetics/pharmacodynamics (PK/PD) approach (mode of administration, dose, and frequency but also absorption, distribution, metabolism, and elimination) to be sure about penetration into bone tissue and the ability to eradicate bacteria growing in a biofilm? Indeed, genomic analysis revealed specific sequences compared to those of other Cutibacterium species and the ability to produce a biofilm structure according to the description of a gene cluster encoding exopolysaccharide production, suspected to be involved in strong adherence, as previously described for C. acnes (74). Interestingly, and recently in my experience, it has been observed that C. avidum can be involved in shoulder prosthesis infection, probably leading to a chronic status (years) according to its ability to resist antibiotics and to evade the immune system.…”

“…The change in behavior (from planktonic cells to an aggregated state or sessile form) is activated by a mechanism of chemical communication that differs between species (73). Biofilm formation has been well studied and characterized for different clinical strains of Cutibacterium species, especially C. acnes (6,51,74,75). To study the ability of C. acnes strains to produce such a structure, various experiments were performed in vitro.…”

Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors

“…Though mouse cancer models have contributed to our understanding of cancer biology, several limitations remain, such as restricted subset of tumour types, limited recapitulation of de novo human tumour development, and drug response, thus inhibiting our capacities to develop corresponding gene therapies [104]. Various animal models have been developed to study particular aspects of the disease; however, they must be used in collection to have any predictive validity in potential gene therapy [105- 107]. These shortcomings demonstrate the challenge with animal models beyond providing basic scientific studies and preliminary screening procedures.…”