PT  - JOURNAL ARTICLE
AU  - Rachel M. Kratofil
AU  - Trevor E. Randall
AU  - Josefien W. Hommes
AU  - Rehnuma Sejuty
AU  - Jessica Chisholm
AU  - Deepa Raju
AU  - Mario Vargas
AU  - P. Lynne Howell
AU  - Gerald B. Pier
AU  - Douglas W. Morck
AU  - Joe J. Harrison
AU  - Paul Kubes
TI  - PNAG exopolysaccharide eradication gives neutrophils access to <em>Staphylococcus aureus</em> biofilm infections
AID  - 10.1101/2023.01.23.525131
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.23.525131
4099  - http://biorxiv.org/content/early/2023/01/23/2023.01.23.525131.short
4100  - http://biorxiv.org/content/early/2023/01/23/2023.01.23.525131.full
AB  - Staphylococcus 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 infection in vivo is necessary to inform new therapeutics. Using a mouse model of S. aureus foreign-body skin infection and intravital microscopy, we imaged the interactions between neutrophils and S. aureus biofilm. 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 the icaADBC operon. Infection with icaADBC-deficient S. aureus strains 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 shelters S. aureus biofilms from innate host defense, and that targeting the biofilm matrix with glycoside hydrolases is a promising therapeutic avenue to treat S. aureus biofilm infections.Author Summary Staphylococcus aureus is 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 the S. aureus biofilm matrix in vivo. Disrupting the biofilm matrix with PgaB gives neutrophils access to bacteria for elimination.Competing Interest StatementThe authors have declared no competing interest.