AUTHOR=Xie Xiaoying , Liu Xiaoqiang , Li Yanling , Luo Ling , Yuan Wenchang , Chen Baiji , Liang Guoyan , Shen Rui , Li Hongyu , Huang Songyin , Duan Chaohui 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01479

DOI=10.3389/fmicb.2020.01479

ISSN=1664-302X

ABSTRACT=<p>Bacterial biofilms do serious harm to the diabetic foot ulcer (DFU) because they play a crucial role in infection invasion and spread. <italic>Staphylococcus aureus</italic>, the predominant Gram-positive bacteria in diabetic foot infection (DFI), is often associated with colonization and biofilm formation. Through biofilm formation tests <italic>in vitro</italic>, we observed that <italic>S. aureus</italic> bacteria 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 of <italic>S. aureus</italic> in clinical isolates and laboratory strains <italic>in vitro</italic>, including a methicillin-resistant strain. Analysis of biofilm components demonstrated that the biofilms formed mainly by increasing extracellular DNA (eDNA) release; remarkably, the <italic>S. aureus</italic> global regulator <italic>sigB</italic> was upregulated, and its downstream factor <italic>lrgA</italic> was downregulated after AGE treatments. Mechanism studies using a <italic>sigB</italic>-deleted mutant (Newman-Δ<italic>sigB</italic>) confirmed that AGEs decreased expression of <italic>lrgA</italic> via induction of <italic>sigB</italic>, which is responsible for eDNA release and is a required component for <italic>S. aureus</italic> biofilm development. In conclusion, the present study suggests that AGEs promote <italic>S. aureus</italic> biofilm formation via an eDNA-dependent pathway by regulating <italic>sigB</italic>. The data generated by this study will provide experimental proof and theoretical support to improve DFU infection healing.</p>