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Antibiotics (Basel, Switzerland) Feb 2021Cyadox has potential use as an antimicrobial agent in animals. However, its pharmacodynamic properties have not been systematically studied yet. In this study, the in...
Cyadox has potential use as an antimicrobial agent in animals. However, its pharmacodynamic properties have not been systematically studied yet. In this study, the in vitro antibacterial activities of cyadox were assayed, and the antibacterial efficacy of cyadox against facultative anaerobes was also determined under anaerobic conditions. It was shown that and (MIC = 0.25 and 1 μg/mL) from pigs, and from poultry, , spp., and from fish were highly susceptible to cyadox (MIC= 1 and 8 μg/mL). However, has no killing effect for drug tolerance. Under in vitro anaerobic conditions, the antibacterial activity of cyadox against most facultative anaerobes was considerably enhanced Under anaerobic conditions for the facultative anaerobes, susceptible bacteria were , . (including , , , , and , excluding ), , spp. (including , , and ), , , , , , and (MICs were 0.25~8 μg/mL, MBCs were 1-64 μg/mL). Intermediate bacteria were spp. (including and ), , and spp. (MICs mainly were 8~32 μg/mL, MBCs were 16~128 μg/mL). This study firstly showed that cyadox had strong antibacterial activity and had the potential to be used as a single drug in the treatment of bacterial infectious diseases.
PubMed: 33546407
DOI: 10.3390/antibiotics10020153 -
NPJ Biofilms and Microbiomes Apr 2024Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there...
Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch's postulates. Correspondingly, we precisely designed four antagonistic strains: Ruegeria lacuscaerulensis, Nioella nitratireducens, Bacillus subtilis and Streptomyces euryhalinus in a ratio of 4:3:2:1, which efficiently guarded against WFS. Dietary supplementation of the probiotics stimulated beneficial gut populations, streptomycin, short chain fatty acids, taurine metabolism potentials, network stability, tight junction, and host selection, while reducing turnover rate and average variation degree of gut microbiota, thereby facilitating ecological and mechanical barriers against pathogens. Additionally, shrimp immune pathways, such as Fcγ R-mediated phagocytosis, Toll-like receptor and RIG-I-like receptor signaling pathways conferring immune barrier, were activated by probiotics supplementation. Collectively, we establish an updated framework for precisely validating co-infection with multiple pathogens and rationally designing antagonistic probiotics. Furthermore, our findings uncover the underlying beneficial mechanisms of designed probiotics from the probiotics-gut microbiome-host immunity axis.
Topics: Humans; Gastrointestinal Microbiome; Coinfection; Feces; Probiotics
PubMed: 38605016
DOI: 10.1038/s41522-024-00509-5 -
Bioorganic & Medicinal Chemistry Aug 2021Apremilast is an important active pharmaceutical ingredient that relies on a resolution to produce the key chiral amine intermediate. To provide a new catalytic and...
Apremilast is an important active pharmaceutical ingredient that relies on a resolution to produce the key chiral amine intermediate. To provide a new catalytic and enzymatic process for Apremilast, we performed the directed evolution of the amine transaminase fromVibriofluvialis. Six rounds of evolution resulted in the VF-8M-E variant with > 400-fold increase specific activity over the wildtype enzyme. A homology model of VF-8M-E was built and a molecular docking study was performed to explain the increase in activity. The purified VF-8M-E was successfully applied to produce the key chiral amine intermediate in enantiopure form and 49% conversion via a kinetic resolution, representing a new enzymatic access towards Apremilast.
Topics: Amines; Biocatalysis; Kinetics; Molecular Structure; Thalidomide; Transaminases; Vibrio
PubMed: 34171757
DOI: 10.1016/j.bmc.2021.116271