A catalytic machine and multiple defense pathways in Paenarthrobacter sp. X6 for sulfamethizole detoxification.

To address the global challenge of sulfonamide antibiotic (SAs) pollution, this study elucidated the efficient removal mechanism and systemic resistance strategies of Paenarthrobacter sp. X6 against sulfamethizole (SMI) using proteome integral solubility alteration (PISA) technology. The strain demonstrated 100 % removal of 10-100 mg/L SMI within 18-33 h, which was achieved by biodegradation (>99 % contribution). The maximum specific removal rate (μm) reached 26.09 mg·L⁻¹ ·h⁻¹ . When using sodium acetate as the carbon source, complete removal (100 %) of 100 mg/L SMI was achieved within 15 h (54.5 % reduction in removal duration). PISA analyses identified a folate metabolism-driven cascade catalytic pathway. Activation of MarR transcriptional regulator may upregulate glycine cleavage enzyme GcvH and dihydropterin kinase FolK to drive efficient SMI removal. Furthermore, the study elucidated multiple sophisticated resistance mechanisms employed by Paenarthrobacter sp. X6. This work provides novel microbial resource featuring dual "biodegradation-resistance" mechanisms for sulfonamide pollution control, blocking antibiotic resistance gene transmission chains.