Lactobacillus rhamnosus GR-1 Coameliorates Tight Junction Disruption and NLRP3-Mediated Inflammation in Drug-Resistant Trueperella pyogenes Infection

Abstract

Antibiotic overuse in dairy farming promotes drug-resistant pathogens, reducing treatment efficacy and causing economic losses. Trueperella pyogenes, a primary causative agent of postpartum endometritis in dairy cows, is increasingly linked to multidrug resistance. This study evaluated Lactobacillus rhamnosus GR-1 (LGR-1) as a nonantibiotic intervention against resistant isolate TP11804 (resistant to 8 antibiotics). Using bovine endometrial epithelial cells and a mouse model, LGR-1 pretreatment mitigated TP1804-induced damage, preserved tight-junction proteins (ZO-1, claudin-1, occludin) and epithelial barrier integrity, and inhibited NLRP3 inflammasome activation (reducing NLRP3, ASC, caspase-1, GSDMD, IL-1β, IL-18). LGR-1 coameliorates tight junction disruption and NLRP3 inflammasome activation, indicating a close association between these two processes. By identifying LGR-1 as a potential substitute for antibiotics in the control of drug-resistant T. pyogenes infections, this research lays a groundwork for providing a theoretical basis for the research and development of antibiotic alternative drugs.