GlmS plays a key role in the virulence factor expression and biofilm formation ability of Staphylococcus aureus promoted by advanced glycation end products

• Published in: Virulence Vol. 15; no. 1; p. 2352476
• Main Authors: Ni, Lijia, Shen, Rui, Luo, Hua, Li, Xuexue, Zhang, Xiaofan, Huang, Lisi, Deng, Yawen, Liao, Xiaoyan, Wu, Yonglin, Duan, Chaohui, Xie, Xiaoying
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: advanced glycation end products; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; biofilm formation; Biofilms - growth & development; Gene Expression Regulation, Bacterial; GlmS-sigB regulatory axis; Glycation End Products, Advanced - metabolism; Humans; Sigma Factor - genetics; Sigma Factor - metabolism; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - pathogenicity; virulence factor expression; Virulence Factors - genetics; GlmS-sigB regulatory axis; biofilm formation; advanced glycation end products; virulence factor expression; Staphylococcus aureus
• ISSN: 2150-5594; 2150-5608; 2150-5608
• DOI: 10.1080/21505594.2024.2352476

is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via upregulation in , contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of in stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of . We constructed NCTC 8325 ∆ for further validation. qRT-PCR analysis revealed that AGEs promoted both and expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆ . NCTC 8325 ∆ showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of and expression, and less and sparser biofilms, indicated that and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆ . Our data extend the understanding of GlmS in the global regulatory network of and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates and plays a significant role in mediating biofilm formation and virulence factor expression.