DnaK-Mediated Protein Deamidation: a Potential Mechanism for Virulence and Stress Adaptation in Cronobacter sakazakii.

Ping Lu, Juan Xue, Xi Chen, Xuemeng Ji

Applied and environmental microbiology 2023 Jul 26

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Cronobacter sakazakii is a Gram-negative bacterium that causes infections in individuals of all ages, with neonates being the most vulnerable group. The objective of this study was to explore the function of the dnaK gene in C. sakazakii and to elucidate the impact of alterations in the protein composition regulated by dnaK on virulence and stress adaptation. Our research demonstrates the critical role of the dnaK gene in various key virulence factors, including adhesion, invasion, and acid resistance in C. sakazakii. Through the use of proteomic analysis, we discovered that deletion of the dnaK gene in C. sakazakii leads to an upregulation of protein abundance and increased levels of deamidated posttranscriptional modifications, suggesting that DnaK may play a role in maintaining proper protein activity by reducing protein deamidation in bacteria. These findings indicate that DnaK-mediated protein deamidation may be a novel mechanism for virulence and stress adaptation in C. sakazakii. These findings suggest that targeting DnaK could be a promising strategy for developing drugs to treat C. sakazakii infections. IMPORTANCE Cronobacter sakazakii can cause disease in individuals of all ages, with infections in premature infants being particularly deadly and resulting in bacterial meningitis and sepsis with a high mortality rate. Our study demonstrates that dnaK in Cronobacter sakazakii plays a critical role in virulence, adhesion, invasion, and acid resistance. Using proteomic analysis to compare protein changes in response to dnaK knockout, we found that dnaK knockout significantly upregulates the abundance of some proteins but also results in the deamidation of many proteins. Our research has identified a connection between molecular chaperones and protein deamidation, which suggests a potential future drug development strategy of targeting DnaK as a drug target.

Citation

Ping Lu, Juan Xue, Xi Chen, Xuemeng Ji. DnaK-Mediated Protein Deamidation: a Potential Mechanism for Virulence and Stress Adaptation in Cronobacter sakazakii. Applied and environmental microbiology. 2023 Jul 26;89(7):e0050523