Pathogenesis and toxinsPropionibacterium acnes biofilm – A sanctuary for Staphylococcus aureus?
Introduction
Propionibacterium acnes is an aerotolerant Gram-positive bacillus found commensally and asymptomatically in and on the skin of humans, especially in the sebaceous glands of oily skin on the face, chest, and back; P. acnes may contribute to the inflammatory component of comedonal acne [1], [2], [3]. P. acnes is frequently isolated from clinical specimens, and, although it is most commonly considered a contaminant, it is increasingly recognized as a primary pathogen [4], [5], especially in shoulder arthroplasty infections [6]. The pathogenesis of P. acnes infections is poorly understood, and such infections do not always manifest clinical characteristics of other bacterial infections, such as elevated white blood count, eythrocyte sedimentation rate or C-reactive protein.
An interesting clinical observation is that, when recovered from clinical specimens, P. acnes may be co-isolated with Staphylococcus species, including Staphylococcus aureus and Staphylococcus epidermidis [7], [8], [9], [10], [11], [12]. While this may be a simple matter of probability since these organisms are often found together as commensal flora, it may alternatively be that the combination of organisms is found together due to mutualism. When cultured with P. acnes, for example, S. aureus manifests a greater degree of β-hemolysis than when grown alone [13]. And, P. acnes produces extracellular coproporphyrin III, which induces aggregation and biofilm formation of S. aureus isolated from skin sources [14]. These observations suggest that there may be a relationship between P. acnes and S. aureus; given their co-isolation from prosthetic joints and cerebrospinal fluid shunts, this interaction may be particularly germane to biofilm-associated infections. Further, if P. acnes enhances the virulence of other pathogens, its presence in clinical specimens may have greater significance than previously appreciated.
A challenge in the culture-based diagnosis of P. acnes infection is that P. acnes grows slowly and preferentially under anaerobic conditions [15]. That anaerobic organisms, including P. acnes, can cause bone and joint infections, suggests that the environment at these infection sites may be anaerobic, as high oxygen tensions would not permit robust growth of anaerobes. Room air at sea level has an average FiO2 of 21%. Oxygen levels in human cartilage have been estimated to range from 1 to 6% [16], and, oxygen tension has been noted to be lower in diseased compared to healthy joints [17], [18].
Culture-based diagnosis and study of aerobic pathogens such as S. aureus typically involves growth under ideal, usually aerobic, conditions. Although many of these organisms are able to grow anaerobically, their growth characteristics, including their ability to form biofilms, under anaerobic conditions, and how they interact with other bacteria under conditions of anaerobiosis, have not been well-defined. Even though it has been broadly observed that organisms interact with symbiotic relationships and complex signaling networks, this is best described for gut and environmental flora. Herein, we evaluated planktonic growth and biofilm formation of P. acnes and S. aureus alone and in combination under aerobic and anaerobic conditions.
Section snippets
Methods
P. acnes IDRL-7676 and S. aureus IDRL-4284, both of which are clinical isolates, were grown on sheep blood agar. S. aureus required 24 h of growth aerobically; P. acnes required 48 h of growth anaerobically. A 1 McFarland solution of each organism was prepared and diluted 1:50 with brain heart infusion (BHI) broth supplemented with 1% glucose. Each organism, or combination of organisms (detailed below), was prepared in quadruplicate in 96-well flat-bottom tissue culture plates. Experimental
Results
When grown planktonically under aerobic conditions, S. aureus demonstrated an expected growth pattern, and as expected, P. acnes showed little growth (Fig. 1). The mixture of the two followed the growth curve of S. aureus. When S. aureus was added to P. acnes, the growth curve mirrored that of S. aureus. Under aerobic conditions, biofilm formation recapitulated planktonic findings except that the OD492 tended to fall after rising (Fig. 2).
When cultured under anaerobic conditions, both organisms
Discussion
Biofilm formation plays a role in device-associated infections, such as prosthetic joint infection, making these infections challenging to cure. P. acnes is a biofilm-forming organism frequently found in culture, sometimes in the setting of other organisms, and often dismissed as a contaminant. The environment of the prosthetic joint space likely has a low oxygen content [16], [17], [18]. Aerobic bacteria and interactions of aerobic and anaerobic bacteria are infrequently studied under
Acknowledgements
We thank James M. Steckelberg, MD, for providing content review. R.P. is supported by the National Institutes of Health [grant numbers R01 AR056647 and R01 AI91594].
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