Yinhuapinggan granules enhance cefotaxime efficacy and alleviate inflammation in extended-spectrum beta-lactamase-producing Escherichia fergusonii infections.

Abstract

OBJECTIVE: This study aimed to investigate the antimicrobial and anti-inflammatory effects of Yinhuapinggan Granules (YHPG) in combination with cefotaxime (CTX) against extended-spectrum beta-lactamase-producing Escherichia fergusonii (ESBL-EF), focusing on how YHPG enhances antibiotic efficacy and modulates inflammatory pathways associated with acute lung injury (ALI). METHODS: The antimicrobial activity of YHPG and CTX was assessed by measuring the minimum inhibitory concentration (MIC) of CTX in the presence of YHPG. qRT-PCR was used to detect the expression of bacterial resistance genes, including acrA, acrB, tolC, OXA-2, TEM-1, and outer membrane porins ompC and ompF. Outer membrane permeability was evaluated using AKP and Bradford assays, while biofilm disruption was analyzed by laser confocal microscopy. In vivo, the effects of YHPG were evaluated in a mouse pneumonia model induced by ESBL-EF infection, including lung index, histopathological changes, and inflammatory cytokine levels. Inflammatory cytokine levels were measured in serum, and the expression of key genes in the NLRP3 inflammasome pathway was analyzed by qRT-PCR. RESULTS: The combination of YHPG and CTX significantly inhibited the growth of ESBL-EF and enhanced its outer membrane permeability. Additionally, YHPG modulated the expression of key bacterial resistance genes, including acrA, acrB, tolC, OXA-2, and TEM-1, as well as the outer membrane porins ompC and ompF. YHPG also effectively disrupted the biofilm structure of ESBL-EF, reducing its protective barrier. In vivo, YHPG treatment alleviated pulmonary inflammation and tissue damage in mice. Serum levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, were significantly reduced, indicating a potent anti-inflammatory effect. Furthermore, YHPG inhibited the activation of the NLRP3-ASC-CASP1-GSDMD signaling pathway, further mitigating inflammation and tissue damage associated with ESBL-EF infection. CONCLUSION: YHPG enhances the antibacterial activity of CTX against ESBL-EF by increasing membrane permeability, disrupting biofilms, and modulating the inflammatory response. This study suggests that YHPG could serve as an adjunctive treatment for antibiotic-resistant infections, offering a promising approach to combat bacterial resistance and inflammation associated with ESBL-EF infections.