Paracetamol modulates bioflm formation in Staphylococcus aureus clonal complex 8 strains

Staphylococcus aureus bioflms are a major problem in modern healthcare due to their resistance to immune system defenses and antibiotic treatments. Certain analgesic agents are able to modulate S. aureus bioflm formation, but currently no evidence exists if paracetamol, often combined with antibiotic treatment, also has this efect. Therefore, we aimed to investigate if paracetamol can modulate S. aureus bioflm formation. Considering that certain regulatory pathways for bioflm formation and virulence factor production by S. aureus are linked, we further investigated the efect of paracetamol on immune modulator production. The in vitro bioflm mass of 21 S. aureus strains from 9 genetic backgrounds was measured in the presence of paracetamol. Based on bioflm mass quantity, we further investigated paracetamol-induced bioflm alterations using a bacterial viability assay combined with N-Acetylglucosamine staining. Isothermal microcalorimetry was used to monitor the efect of paracetamol on bacterial metabolism within bioflms and green fuorescent protein (GFP) promoter fusion technology for transcription of staphylococcal complement inhibitor (SCIN). Clinically relevant concentrations of paracetamol enhanced bioflm formation particularly among strains belonging to clonal complex 8 (CC8), but had minimal efect on S. aureus planktonic growth. The increase of bioflm mass can be attributed to the marked increase of N-Acetylglucosamine containing components of the extracellular matrix, presumably polysaccharide intercellular adhesion. Bioflms of RN6390A (CC8) showed a signifcant increase in the immune modulator SCIN transcription during co-incubation with low concentrations of paracetamol. Our data indicate that paracetamol can enhance bioflm formation. The clinical relevance needs to be further investigated.