Staphylococcus aureus nuclease: a target for infection detection and biofilm prevention

The usage of biomedical implants is currently rapidly increasing due to ageing populations. Consequently, the number of biomaterial-associated infections increases, which challenges healthcare systems around the globe. One of the main causative agents is the bacterium Staphylococcus aureus. S. aureus-mediated biomaterial-associated infections are hard to overcome both by our own immune system and by antibiotic therapy. This is attributed to antimicrobial resistance, the ability of S. aureus to skew and evade the immune system, and to the formation of biofilms. Biofilms are layers of polysaccharides, proteins and extracellular DNA that shelter the bacteria from the immune system and antimicrobial agents. S. aureus produces a DNA-degrading enzyme (nuclease), which has two major effects. Firstly, nuclease degrades DNA in the biofilm. Secondly, nuclease degrades neutrophil extracellular traps. These are DNA-based nets coated with antimicrobial peptides that neutrophils produce during inflammatory responses to pathogens and foreign materials. Nuclease could thus affect the S. aureus biofilm integrity, uncovering the embedded bacteria. However, animal studies showed that S. aureus bacteria unable to produce nuclease are less capable of forming biomaterial-associated infections. Furthermore, a nuclease-activated fluorescent probe was shown to detect S. aureus in vitro with high sensitivity. Lastly, it was observed that low concentrations of certain antibiotics reduce nuclease production by S. aureus, possibly leading to impaired biofilm formation. Together, these observations imply that nuclease is a facile marker to detect S. aureus infections and may serve as a target to treat biomaterial-associated infections. However, this might have an inherent risk of eliciting antimicrobial resistance