The emergence of multidrug-resistant gram-negative bacteria poses a severe threat to global public health, and the limitations of traditional antibiotics in efficacy and drug resistance have become increasingly prominent. This study integrated AI technologies, including RFdiffusion and ProteinMPNN, to design and screen a novel antimicrobial peptide, AMP-ZJLC586, which exhibited potent antimicrobial activity against multidrug-resistant gram-negative bacteria, with a minimum inhibitory concentration (MIC) ranging from 0.5 to 8 μg/mL, and has the characteristics of high stability and low cytotoxicity. In addition, it can also kill clinically isolated drug-resistant bacteria and inhibit the formation of their biofilms. In terms of bactericidal mechanism, AMP-ZJLC586 can reduce the production of bacterial ATP by inhibiting the synthesis of lipopolysaccharide and the enzyme activity of respiratory chain, and oxidative stress response and SOS response at the same time. In the sepsis mouse model, AMP-ZJLC586 significantly increased the survival rate by 65%, effectively suppressed the level of inflammatory factors, improved organ damage, and reduced the bacterial load of target organs by 103-104 CFU/g, highlighting its great therapeutic potential.
Yan Zhang, Xin-Yuan Zhang, Xiao-Jie Chen et al.· European journal of medicina...· 0 citations
With the increasing prevalence of antibiotic–heavy metal co-contamination in agricultural wastewater, elucidating the antibiotic removal capacity of degrading bacteria under heavy metal stress, as well as their adaptive mechanisms, is of considerable theoretical significance and practical value. In this study, the highly efficient TYL-degrading strain TYL-A1 was selected as a model organism, and the effects of Pb2+ exposure on its TYL removal performance, oxidative stress response, cell surface characteristics, and transcriptional regulation were systematically investigated. The results showed that TYL removal remained above 85% after 72 h under a nominal Pb2+ concentration of 100 mg/L in the phosphate-containing MSM system. The phosphate may have reduced Pb2+ bioavailability. Nominal Pb2+ exposure increased the activities of superoxide dismutase (SOD) and catalase (CAT), accompanied by elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as a decrease in adenosine triphosphate (ATP) content. This indicates that the strain experienced pronounced oxidative stress and altered energy metabolism. Meanwhile, cell membrane permeability increased. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) analyses showed that the overall cellular morphology remained intact, whereas the membrane surface structure and related cellular components underwent adaptive changes. According to a transcriptomic analysis, the differentially expressed genes were mainly enriched in pathways associated with primary metabolism, transmembrane transport, ABC transporters, and two-component systems. In summary, strain TYL-A1 maintained high TYL removal performance under the tested nominal Pb2+ concentrations in the present phosphate-containing culture system, suggesting its potential applicability in the bioremediation of water bodies co-contaminated with antibiotics and heavy metals.
Ye Wang, Heshi Tian, Xi-Qing Zhang et al.· Antioxidants· 0 citations
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