Proteomics

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


ABSTRACT: Staphylococcus aureus (S. aureus) 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 hyperglycemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus, contributing to the high morbidity and mortality of diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used a pull-down assay and LC‒MS/MS to identify the GlmS protein as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB. We constructed Newman ∆glmS for further validation. Quantitative RT‒PCR analysis revealed that AGEs promoted both glmS and sigB expression in the Newman strain but had no effect on Newman ∆glmS. Newman ∆glmS showed a significant attenuation in biofilm formation ability and virulence, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased hemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in Newman ∆glmS. Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which subsequently directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Staphylococcus Aureus

SUBMITTER: RUI SHEN  

LAB HEAD: Xiaoying Xie

PROVIDER: PXD046076 | Pride | 2024-05-22

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
AGE-DPD.mgf Mgf
AGE-DPD.raw Raw
BSA-DPD.mgf Mgf
BSA-DPD.raw Raw
F002371.csv Csv
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Publications

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

Ni Lijia L   Shen Rui R   Luo Hua H   Li Xuexue X   Zhang Xiaofan X   Huang Lisi L   Deng Yawen Y   Liao Xiaoyan X   Wu Yonglin Y   Duan Chaohui C   Xie Xiaoying X  

Virulence 20240513 1


<i>Staphylococcus aureus (S. aureus)</i> 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 <i>sigB</i> upregulation in <i>S. aureus</i>, contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection.  ...[more]

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