Selection of biofilm-inhibiting ssDNA aptamers against antibiotic-resistant Edwardsiella tarda by inhibition-SELEX and interaction with their binding proteins

Article

Author: Yan, Qingpi ; Huang, Lixing ; Wang, Jiaen ; Fan, Yunting ; Tan, Ying ; Weng, Qibiao ; Zheng, Jiang

Biofilms can increase bacterial resistance to antibiotic therapies. Edwardsiella tarda with biofilm is highly resistant to antibacterial treatment, especially for the antibiotic-resistant strain. In this study, we obtained biofilm-inhibiting aptamers against antibiotic-resistant E. tarda via a novel systematic evolution of ligands by exponential enrichment (SELEX) technique, called inhibition-SELEX. After four rounds of screening and validation, we identified aptamers IB1, IB2, and IB3, which demonstrated biofilm-inhibition and biofilm-degradation rates of 69 %, 75 %, and 62 % and 51 %, 63 %, and 45 % at 2 μmol/L, respectively, against antibiotic-resistant E. tarda. Magnetic separation, SDS-PAGE, and mass spectrometry analyses revealed that all three aptamers could bind to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), while IB2 could also bind to formate C-acetyltransferase (FA). Through molecular docking and molecular dynamics simulations, it was found that the four complexes primarily interact through hydrogen bonding. Among them, IB1-GAPDH exhibited the strongest stability, followed by IB2-FA, then IB2-GAPDH, and IB3-GAPDH was the least stable. Our results suggest that IB1, IB2, and IB3 may inhibit and degrade E. tarda biofilm by interfering with the synthesis, secretion, and transportation of its extracellular polysaccharides and proteins by interacting with GAPDH and FA.

01 Jun 2024·Bioorganic Chemistry

Novel CCR3-targeted cyclic peptides as potential therapeutic agents for age-related macular degeneration via inhibiting angiogenesis and reducing retinal photoreceptor damage

Article

Author: Guan, Yonghui ; Fan, Wen ; Qian, Hai ; Li, Yuanyuan ; Wan, Jiale ; Jiang, Hongyu ; Chen, Qin ; Lin, Haiyan ; Shi, Wei ; Guo, Shu'ai ; Luo, Chenghui ; Wu, Xinjing

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.

01 Dec 2018·Poultry ScienceQ2 · AGRICULTURAL & FORESTRY SCIENCE

Safety and efficacy of attenuated classic and variant 2 infectious bronchitis virus candidate vaccines

Q2 · AGRICULTURAL & FORESTRY SCIENCE

ArticleOA

Author: Ali, Ahmed ; Kilany, Walid H ; Elkady, Magdy ; Zain El-Abideen, Mohamed A ; Sayed, Magdy El

Vaccination programs against infectious bronchitis virus (IBV) in Egypt depend on both classical and/or imported variant IBV strain vaccines. However, many IBV outbreaks associated with respiratory distress, nephropathy, and high mortalities were attributed to the circulation of both classical and new nephropathogenic IBV variant 2 strains. In the present study, we report the development of attenuated IBV candidate vaccines using the classic IBV strains (IBM41 and IB2) and a nephropathogenic strain (IBvar2). The wild-type (WT) viruses were attenuated through serial passages in embryonated specific pathogen free (SPF) chicken eggs. Virulence of the attenuated viruses was then tested via the ocular route inoculation and the in vivo back passage in day-old SPF chickens. Efficacy against homologous challenge was investigated also in day-old SPF chickens. Results showed that the viruses were successfully adapted to the embryo by the 100th (IBM41 and IB2) and 110th passages (IBvar2). The attenuated viruses were safe and showed no change of virulence in day-old SPF chickens up to the 10th back passages. The efficacy experiment showed that the attenuated vaccines showed 90 to 100% protection against the homologous challenge based on ciliostasis score and protection percent. The att-IBM41 and att-IB2 vaccines were able to reduce the shedding of the challenge at 3 days post-infection (DPI) and no virus shedding was detected in both vaccinated groups by 5 DPI. In the att-IBvar2 vaccinated birds, only 20% of vaccinated birds shed the challenge virus with low titers (102.10±0.3 EID50/mL) at 3 DPI. In conclusion, the attenuated strains IBM41, IB2, and IBvar2 are efficient vaccine candidates against currently circulating classic and variant IB viruses, respectively. Further studies to evaluate the field efficacy and combining these attenuated IBV strains to induce a wider protection against heterologous IBV challenge are suggested.

100 Deals associated with IB-2(China Pharmaceutical University)

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Indication	Highest Phase	Country/Location	Organization	Date
Age Related Macular Degeneration	Preclinical	China	China Pharmaceutical University	01 Jun 2024

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