Jing Xu

The opportunistic pathogen Pseudomonas aeruginosa poses a serious threat to immunocompromised patients. Monosodium glutamate (MSG), a widely used flavor enhancer, has been reported to possess anti-inflammatory and antioxidant properties. However, its therapeutic potential and mechanism against Pseudomonas aeruginosa (P. aeruginosa) infection have remained unexplored. This study systematically elucidated the protective effects and molecular mechanisms of MSG against P. aeruginosa-induced acute lung injury (ALI). In a murine pneumonia model, MSG administration effectively alleviated lung pathological damage, edema, and inflammatory responses. Mechanistically, MSG exerted protection through a multifaceted strategy, including direct suppression of bacterial virulence via binding to PopB of T3SS inhibition of the TLR4/MyD88/MAPK-driven inflammatory cascade and pro-inflammatory cytokine production, enhancement of endogenous antioxidant defense (SOD, CAT), and reshaping of pulmonary macrophages from the M1 to M2 phenotype. Notably, the anti-virulence effect of MSG, achieved by binding to PopB (K_D = 3.52 × 10⁻⁶ M), presented a distinct advantage over traditional antimicrobials by potentially mitigating resistance development. Collectively, these findings indicated that MSG can alleviate ALI caused by P. aeruginosa infection.

The coexistence of antibiotic resistance genes (ARGs), particularly those conferring resistance to last-resort antibiotics, is increasingly present in lesser-studied bacterial species. Tigecycline is currently one of the last important barriers in the treatment of carbapenem-resistant bacterial infections, whose resistance gene, tet(X), is prevalent across multiple bacterial genera, but the coexistence of tet(X3) and tet(X4) in Acinetobacter sp. is rarely observed. Here, we report a strain co-harboring the chromosomal tet(X3) and plasmid-borne tet(X4) isolated from a commercial beef cattle farm in Henan province, China. The strain exhibited resistance to ampicillin, gentamicin, chloramphenicol, sulfamethoxazole, tetracycline, doxycycline, tigecycline, and omadacycline. Based on whole-genome sequencing (WGS), the strain was identified as A. indicus using Average Nucleotide Identity (ANI) and digital DNA–DNA hybridization (dDDH). Chromosomal tet(X3) was identified in the genetic context, ISVsa3-XerD-tet(X3)-res-ISVsa3. The plasmid-located tet(X4) with the genetic context, ISVsa3-abh-tet(X4)-ISVsa3, and 14 additional resistance genes were located in multiple pdif modules. Two different typing methods, the Rep-based strategy (designed for A. baumanii) and MOB-typer, identified the tet(X4)-positive plasmid as GR31 and rep_cluster_1656, respectively. Conjugation assay failed to observe the transfer of the tet(X4)-positive plasmid into recipients, E. coli J53 and Salmonella LGJ2. The co-occurrence of tet(X3) and tet(X4) in Acinetobacter may suggest a risk of rapid dissemination of tigecycline resistance and the hidden presence of numerous undetected bacteria co-carrying high-risk ARGs in the agroecological system, both of which should cause particular concern.

Escherichia coli (E. coli) is a severe foodborne pathogen, and the formation of its biofilm can enhance bacterial virulence and reduce antibiotic sensitivity, posing a significant threat to human and animal health. Ferulic Acid (FA) is a natural active product that has been proven to possess various biological activities, including anti-inflammatory, antioxidant, and antitumor properties. This study evaluated the inhibitory effect of FA on the biofilm formation of E. coli through crystal violet (CV) staining and scanning electron microscopy (SEM) and investigated the synergistic effect of FA with antibiotics, using the alamar blue (AB) assay. In addition, the regulatory effect of FA on the transcription of biofilm-related genes was analyzed using qRT-PCR technology. The results showed that FA could significantly inhibit biofilm formation, reduce the production of extracellular polymeric substances (EPS), and weaken bacterial motility, without affecting bacterial growth and metabolic activity. qRT-PCR analysis revealed that FA significantly downregulated the expression of curli-related gene csgD, flagella-related genes (flhC, flhD, and motA), and type I fimbriae gene fimA, while upregulating the transcription of c-di-GMP-related genes (pdeR, pdeA, and dosP). It is noteworthy that FA exhibits significant synergistic antibacterial effects when combined with clinically commonly used antibiotics, including sodium fosfomycin, ceftriaxone, gentamicin, and tetracycline, with the most prominent synergistic effect observed in the combination of FA and sodium fosfomycin. These results confirm that FA possesses notable anti-biofilm activity and novel synergistic antibacterial properties, providing a potential therapeutic strategy for treating E. coli infections.