Advanced Glycation End Products Enhance Biofilm Formation by Promoting Extracellular DNA Release Through sigB Upregulation in Staphylococcus aureus .

Bacterial biofilms do serious harm to the diabetic foot ulcer (DFU) because they play a crucial role in infection invasion and spread.Staphylococcus aureus, the predominant Gram-positive bacteria in diabetic foot infection (DFI), is often associated with colonization and biofilm formation. Through biofilm formation testsin vitro, we observed thatS. aureusbacteria isolated from DFU wounds were more prone to form biofilms than those from non-diabetic patients, while there was no difference in blood sugar between the biofilm (+) diabetics (DB+) and biofilm (-) diabetics (DB-). Furthermore, we found that advanced glycation end products (AGEs) promoted the biofilm formation ofS. aureusin clinical isolates and laboratory strainsin vitro, including a methicillin-resistant strain. Analysis of biofilm components demonstrated that the biofilms formed mainly by increasing extracellular DNA (eDNA) release; remarkably, theS. aureusglobal regulatorsigBwas upregulated, and its downstream factorlrgAwas downregulated after AGE treatments. Mechanism studies using asigB-deleted mutant (Newman-Delta sigB) confirmed that AGEs decreased expression oflrgAvia induction ofsigB, which is responsible for eDNA release and is a required component forS. aureusbiofilm development. In conclusion, the present study suggests that AGEs promoteS. aureusbiofilm formation via an eDNA-dependent pathway by regulatingsigB. The data generated by this study will provide experimental proof and theoretical support to improve DFU infection healing.