TBP-TA exhibits potent antibacterial activity against vancomycin-resistant Enterococcus

Area of Science:

• Microbiology
• Pharmacology
• Veterinary Medicine

Background:

• Antimicrobial resistance (AMR) poses significant threats to livestock health and productivity.
• Small-molecule compounds offer diverse mechanisms for combating bacterial infections.

Purpose of the Study:

• To evaluate the antibacterial efficacy of the small-molecule compound TBP-TA against vancomycin-resistant Enterococcus (VRE).
• To investigate the mechanisms of action and therapeutic potential of TBP-TA in livestock models.

Main Methods:

• In vitro antibacterial assays and in vivo animal models were employed.
• Mechanistic studies included membrane integrity, proton motive force, efflux pump function, and reactive oxygen species analysis.
• Untargeted metabolomics and histopathological analyses were performed.

Main Results:

• TBP-TA demonstrated potent bactericidal activity against VRE by disrupting membrane integrity, dissipating proton motive force, and inducing reactive oxygen species.
• Metabolomic analysis revealed TBP-TA perturbs energy metabolism and antioxidant defenses.
• In a mouse model, TBP-TA significantly reduced VRE colonization and alleviated intestinal injury, outperforming linezolid.

Conclusions:

• TBP-TA exhibits strong bactericidal effects against VRE through multiple mechanisms.
• TBP-TA shows promise as a therapeutic agent for multidrug-resistant bacterial infections in livestock.