{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:50:09Z","timestamp":1791921009495,"version":"4.3.4"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR40142\/BTIS\/137\/72\/2023"],"award-info":[{"award-number":["BT\/PR40142\/BTIS\/137\/72\/2023"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03bcg\/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 \u22122.29 log2 fold change. Molecular docking supported by 100 ns molecular dynamics simulations demonstrated stable ertapenem binding to the PurQ active site (docking score: \u22129.615 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\u2019s 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.<\/jats:p>","DOI":"10.1021\/acsomega.5c11260","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:02:37Z","timestamp":1790834557000},"page":"60668-60679","source":"Crossref","is-referenced-by-count":0,"title":["Ertapenem Exposure\nIs Associated with Downregulation\nof Purine Biosynthesis Proteins and Inhibition of Biofilm Formation\nin\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1021","volume":"11","author":[{"given":"Anamika","family":"Singh","sequence":"first","affiliation":[{"name":"All India Institute of Medical Sciences , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surabhi","family":"Pandit","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-1958","authenticated-orcid":true,"given":"Pradeep","family":"Pant","sequence":"additional","affiliation":[{"name":"Bennett University , , ,","place":["Greater Noida, Uttar Pradesh, India, 201310"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2886-7963","authenticated-orcid":true,"given":"Tej P.","family":"Singh","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata","family":"Sharma","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3826-8064","authenticated-orcid":true,"given":"Pradeep","family":"Sharma","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences , ,","place":["New Delhi, India, 110029"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"2","key":"2026101315094397200_cit1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.azn.2024.11.003","article-title":"Virulence factors in\nbiofilm formation and therapeutic strategies for Staphylococcus aureus: A review","volume":"1","author":"Wang","year":"2025","journal-title":"Anim. 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Resist."},{"issue":"10","key":"2026101315094397200_cit7","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.3390\/molecules30102126","article-title":"Recent Developments\nin Penem Antibiotics: Structural and Therapeutic Perspectives","volume":"30","author":"Rusu","year":"2025","journal-title":"Molecules"},{"key":"2026101315094397200_cit8","doi-asserted-by":"publisher","first-page":"112829","DOI":"10.1016\/j.ejmech.2020.112829","article-title":"\u03b2-lactam\nantibiotics:\nAn overview from a medicinal chemistry perspective","volume":"208","author":"Lima","year":"2020","journal-title":"Eur. J. Med. Chem."},{"issue":"6","key":"2026101315094397200_cit9","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1093\/cid\/ciz995","article-title":"Cefazolin and Ertapenem Salvage Therapy\nRapidly Clears Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia","volume":"71","author":"Ulloa","year":"2020","journal-title":"Clin. Infect. 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Resist."},{"issue":"3","key":"2026101315094397200_cit16","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.00804-21","article-title":"The de\nnovo Purine Biosynthesis Pathway Is the Only Commonly Regulated Cellular\nPathway during Biofilm Formation in TSB-Based Medium in Staphylococcus aureus and Enterococcus faecalis","volume":"9","author":"Ge\u0301linas","year":"2021","journal-title":"Microbiol. 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