2026-10-14T04:40:14Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33977475 2026-09-23T18:14:21Z category_4 category_7 category_8 category_14 category_19 category_21 category_132 category_133 portal_63 item_type_3 month_year_09_2026

A Small Molecule Dual Inhibitor of agr Quorum Sensing and ATP Synthase Blocks Acute and Chronic Virulence Phenotypes in Staphylococcus aureus Troy D. Vulpis (17591804) Jordan T. York (8384808) A.P. Clay (25099548) Thomas J. Polaske (7854698) Samuel W. Markovich (25099551) Kijeong Lee (724815) Douglas H. Chang (12378254) Sean P. Palecek (392158) David M. Lynn (1327461) John-Demian Sauer (494732) Lloyd M. Smith (200274) Helen E. Blackwell (1247094) Biochemistry Medicine Microbiology Molecular Biology Pharmacology Biotechnology Infectious Diseases Plant Biology synthetic small molecule small colony variants single chemical modulator establish chronic infections dual inhibition may chronic virulence phenotypes acute infections caused ablating intracellular survival atp synthase alone atp synthase affects staphylococcus aureus plays agr </ italic atp synthase agr </ staphylococcus aureus work demonstrates sensing system quorum sensing prominent role murine macrophages including hemolysis genetic inactivation efficient clearance dually inhibiting common pathogen biofilm formation antibiotic resistance also show additive effect >) quorum The accessory gene regulator (<i>agr</i>) quorum-sensing system in Staphylococcus aureus plays a prominent role in acute infections caused by this common pathogen. In contrast, ATP synthase affects the ability of S. aureus to establish chronic infections and persist as small colony variants. In this study, we report that a synthetic small molecule, CP-20, is capable of dually inhibiting <i>agr</i> and ATP synthase. We demonstrate CP-20’s ability to counteract key virulence phenotypes associated with both pathways, including hemolysis, biofilm formation, and antibiotic resistance. We also show that CP-20 facilitates more efficient clearance of S. aureus by murine macrophages than genetic inactivation of either <i>agr</i> or ATP synthase alone, suggesting that dual inhibition may have an additive effect on ablating intracellular survival. This work demonstrates the utility of a single chemical modulator to attenuate S. aureus pathogenesis via two nonessential pathways and suggests a pathway toward nonbactericidal virulence control. 2026-09-23T00:00:00Z Dataset Dataset 10.1021/acsinfecdis.6c00432.s002 https://figshare.com/articles/dataset/A_Small_Molecule_Dual_Inhibitor_of_agr_Quorum_Sensing_and_ATP_Synthase_Blocks_Acute_and_Chronic_Virulence_Phenotypes_in_Staphylococcus_aureus/33977475 CC BY-NC 4.0