Disruption of the Staphylococcus aureus biofilm by IsaA.

Abstract

Staphylococcus aureus, a human commensal and pathogen, is capable of forming biofilms on a variety of host tissues and implanted medical devices. Biofilm-associated infections resist antimicrobial chemotherapy and attack from the host immune system, making these infections particularly difficult to treat. To gain insight into environmental conditions that influence S. aureus biofilm development, we screened a library of small molecules for the ability to inhibit S. aureus biofilm formation. This led to the finding that the polyphenolic compound tannic acid inhibits S. aureus biofilm formation in multiple biofilm models without inhibiting bacterial growth. We present evidence that tannic acid inhibits S. aureus biofilm formation via a mechanism dependent upon the putative transglycosylase IsaA. Tannin-containing drinks like tea have been found to reduce methicillin-resistant S. aureus nasal colonization; we found that black tea inhibited S. aureus biofilm development and that an isaA mutant resisted this inhibition. We developed a rodent model for S. aureus throat colonization and found that tea consumption reduced S. aureus throat colonization via an isaA-dependent mechanism. We also showed two distinct mechanisms by which S. aureus adapts to resist tannic acid stress. First, when the dedicated regulator of the Sigma B stress response system, rsbU, is mutated, the cells overproduce extracellular proteases, clearing IsaA from the extracellular milieu. Second, when the serine threonine kinase pknB is mutated, PIA (a major component of the biofilm matrix) is overproduced, which we hypothesize strengthens the overall structure of the matrix, conferring resistance to tannic acid. These findings provide insight into a molecular mechanism by which commonly consumed polyphenolic compounds, such as tannins, influence S. aureus surface colonization, as well as how bacteria can adapt to evade such antibiofilm treatments.