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oai:figshare.com:article/34039042 2026-10-01T05:12:22Z category_1 category_4 category_7 category_8 category_19 category_21 category_873 category_46 category_734 category_64 category_132 category_134 portal_63 item_type_6 month_year_10_2026

Ertapenem Exposure Is Associated with Downregulation of Purine Biosynthesis Proteins and Inhibition of Biofilm Formation in Staphylococcus aureus Anamika Singh (362319) Surabhi Pandit (25152364) Pradeep Pant (6507386) Tej P. Singh (9286476) Sujata Sharma (36250) Pradeep Sharma (59873) Biophysics Biochemistry Medicine Microbiology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer Infectious Diseases Virology treated versus untreated reduce bacterial vulnerability healthcare systems owing biofilms create polymer 10 upregulated ). identified 59 proteins novel antibacterial targets molecular docking supported targeting purine biosynthesis resistant bacterial pathogens purq active site antibiofilm activity correlates purine biosynthesis proteins particularly fgam synthase 2 </ sub mature biofilm formation purine biosynthesis fgam synthase 706 proteins − 2 novel aspect docking score biofilm formation proteins associated − 9 work provides using lc study demonstrates strong foundation significant burden quantified 1 purq ), predominantly downregulated potential inhibitor major cause key residues immune responses fold change first evidence findings implicate essential enzyme derived adherent based matrices antimicrobial agents acquired infections 615 kcal Staphylococcus aureus is a major cause of both nosocomial and community-acquired infections, imposing a significant burden on healthcare systems owing to its capacity for mature biofilm formation. These biofilms create polymer-based matrices that reduce bacterial vulnerability to immune responses and antimicrobial agents, complicating the treatment of drug-resistant S. aureus strains and underscoring the need for novel antibacterial targets. Here, we provide the first evidence that FGAM synthase (PurQ), an essential enzyme in the de novo purine biosynthesis pathway, is a putative intracellular protein target associated with ertapenem exposure in S. aureus. Our study demonstrates that ertapenem exhibits potent antibacterial activity against S. aureus (MIC = 1 μg/mL) and is a potential inhibitor of biofilm formation. Mechanistically, this antibiofilm activity correlates with selective downregulation of purine biosynthesis proteins. Using LC-MS/MS analysis of biofilm-derived adherent S. aureus cells, we quantified 1,706 proteins and identified 59 proteins with statistically significant expression changes in ertapenem-treated versus untreated S. aureus cells (49 downregulated, 10 upregulated). Proteins associated with purine biosynthesis were predominantly downregulated, particularly FGAM synthase (PurQ) with a −2.29 log₂ fold change. Molecular docking supported by 100 ns molecular dynamics simulations demonstrated stable ertapenem binding to the PurQ active site (docking score: −9.615 kcal/mol) through interactions with key residues: Gly53, Asp54, Tyr55, Gln89, His141, Gly142, Glu143, and Gly144. Collectively, these findings implicate a novel aspect of ertapenem’s activity, connected to the disruption of purine biosynthesis in S. aureus through targeted downregulation of FGAM synthase. This work provides a strong foundation for drug repurposing strategies aimed at targeting purine biosynthesis in drug-resistant bacterial pathogens. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acsomega.5c11260.s001 https://figshare.com/articles/journal_contribution/Ertapenem_Exposure_Is_Associated_with_Downregulation_of_Purine_Biosynthesis_Proteins_and_Inhibition_of_Biofilm_Formation_in_Staphylococcus_aureus/34039042 CC BY-NC 4.0