A Supramolecular Antibiotic Targeting Drug-Resistant through the Inhibition of Virulence Factors and Activation of Acquired Immunity.

The bacterium is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHP, which can circumvent the drug resistance mechanism of and effectively combat infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate . Furthermore, dHTSN1@pHP was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHP exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of compared to untreated mice with -infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHP in treating drug-resistant infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant .