PNAG exopolysaccharide eradication gives neutrophils access toStaphylococcus aureusbiofilm infections

Abstract

AbstractStaphylococcus aureus(S. aureus) can form biofilms on biotic or abiotic surfaces making biofilm infections a relevant clinical problem. Biofilms can evade immunity and resist antimicrobial treatment, and as such an understanding of biofilm infectionin vivois necessary to inform new therapeutics. Using a mouse model ofS. aureusforeign-body skin infection and intravital microscopy, we imaged the interactions between neutrophils andS. aureusbiofilm. We observed that neutrophils were separated from bacteria by a biofilm matrix composed of the polysaccharide intercellular adhesin (PIA), an exopolysaccharide chemically designated as poly-N-acetylglucosamine (PNAG) that is produced by enzymatic machinery encoded by theicaADBCoperon. Infection withicaADBC-deficient S. aureusstrains led to increased neutrophil infiltration and access to bacteria and resulted in full clearance of infection by 7 days. Moreover, enzymatic treatment with PgaB, which hydrolyzes partially deacetylated PNAG, was shown to disaggregate the biofilm giving neutrophils access into the infection site to improve clearance. Taken together, our results show that PNAG sheltersS. aureusbiofilms from innate host defense, and that targeting the biofilm matrix with glycoside hydrolases is a promising therapeutic avenue to treatS. aureusbiofilm infections.Author SummaryStaphylococcus aureusis a major cause of biofilm-associated infections, which pose a major threat to human health. A biofilm is difficult to treat since bacteria are protected from antimicrobials within an extracellular matrix. This study is the first to show that the PgaB enzyme, a glycoside hydrolase, can disrupt theS. aureusbiofilm matrix in vivo. Disrupting the biofilm matrix with PgaB gives neutrophils access to bacteria for elimination.