Malintha Abeysiri / Biology / Faculty Mentor: Qing Tang
The emergence and spread of Staphylococcus aureus Methicillin-resistant strain (MRSA) attribute to its resistance to multiple antibiotics and resilience in the changing environment, are posing significant challenges for treatment and infection control strategies. Addressing this urgent healthcare crisis requires a comprehensive understanding of how S. aureus modulates its central metabolism to survive nutrition starvation. In this study, we focus on elucidating the regulatory network governing glutamine metabolism in S. aureus, a fundamental process essential for bacterial growth. We used EMSA, BLI, and qPCR to study how the transcriptional repressor GlnR regulates glutamine metabolism. We found that glutamine synthetase GlnA facilitates GlnR binding to DNA, suppressing glutamine metabolism genes when glutamine is present. However, the regulation of GlnR in the absence of glutamine is unknown. We have identified that the PII-family protein PstA interacts with GlnR. Previous studies have shown that the production of c-di-AMP, the ligand of PstA, is regulated by glutamine availability. We hypothesize that PstA abolishes the GlnA-DNA interaction in the absence of glutamine, leading to the de-repression of glutamine metabolism genes. Our study will improve the understanding of bacterial metabolism regulation, providing insights into targeting central metabolism regulatory proteins as antimicrobial targets, thus advancing infectious disease therapeutics.
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