Crystal structure of UDP-glucose pyrophosphorylase from<i>Yersinia pestis</i>, a potential therapeutic target against plague

Gibbs, Morgan E.; Lountos, G.T.; Gumpena, R.; Waugh, David S.

doi:10.1107/s2053230x19011154

Cited by 6 publications

(2 citation statements)

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“…However, elucidation of this structure could greatly improve in silico modeling and development of novel inhibitors. Currently, the crystal structure of UDPG:PP is only known for several eukaryotes and following bacteria: Helicobacter pylori (PDB codes 3JUJ and 3JUK) ( Kim et al, 2010 ), E. coli (PDB code 2E3D) ( Thoden and Holden, 2007a ), Corynebacterium glutamicum (PDB code 2PA4) ( Thoden and Holden, 2007b ), Acinetobacter baumannii (PDB codes 6IKX and 6IKZ) ( Lee and Kang, 2019 ), Sphingomonas elodea (PDB 2UX8) ( Aragao et al, 2007 ), Erwinia amylovora (PDB code 4D48) ( Benini et al, 2017 ), Yersinia pestis (PDB code 6MNU) ( Gibbs et al, 2019 ), and Burkholderia spp. (PDB codes 5VCT, 5VE7, 5J49, 5I1F) ( Abendroth et al, 2016a , b , 2017a , b ).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

et al. 2020

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Pneumonia, of which Streptococcus pneumoniae is the most common causative agent, is considered one of the three top leading causes of death worldwide. As seen in other bacterial species, antimicrobial resistance is on the rise for this pathogen. Therefore, there is a pressing need for novel antimicrobial strategies to combat these infections. Recently, uridine diphosphate glucose pyrophosphorylase (UDPG:PP) has been put forward as a potential drug target worth investigating. Moreover, earlier research demonstrated that streptococci lacking a functional galU gene (encoding for UDPG:PP) were characterized by significantly reduced in vitro and in vivo virulence. Therefore, in this study we evaluated the anti-virulence activity of potential UDPG:PP inhibitors. They were selected in silico using a tailor-made streptococcal homology model, based on earlier listerial research. While the compounds didn't affect bacterial growth, nor affected in vitro adhesion to and phagocytosis in macrophages, the amount of polysaccharide capsule was significantly reduced after co-incubation with these inhibitors. Moreover, co-incubation proved to have a positive effect on survival in an in vivo Galleria mellonella larval infection model. Therefore, rather than targeting bacterial survival directly, these compounds proved to have an effect on streptococcal virulence by lowering the amount of polysaccharide and thereby probably boosting recognition of this pathogen by the innate immune system. While the compounds need adaptation to broaden their activity to more streptococcal strains rather than being strain-specific, this study consolidates UDPG:PP as a potential novel drug target.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

et al. 2020

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“…The mortality rates are indeed high, with pulmonary plague presenting a mortality rate of 40% and being fatal when untreated [23]. In parallel with B. anthracis, Y. pestis is one of the most virulent and deadliest BWAs, presenting mortality rates of 100% within 3 to 6 days postinfection [21,24,25]. Y. pestis is a nonmotile, non-spore-forming coccobacillus [20].…”

Section: Plaguementioning

confidence: 99%

Recent Trends in Protective Textiles against Biological Threats: A Focus on Biological Warfare Agents

et al. 2022

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The rising threats to worldwide security (affecting the military, first responders, and civilians) urge us to develop efficient and versatile technological solutions to protect human beings. Soldiers, medical personnel, firefighters, and law enforcement officers should be adequately protected, so that their exposure to biological warfare agents (BWAs) is minimized, and infectious microorganisms cannot be spread so easily. Current bioprotective military garments include multilayered fabrics integrating activated carbon as a sorptive agent and a separate filtrating layer for passive protection. However, secondary contaminants emerge following their accumulation within the carbon filler. The clothing becomes too heavy and warm to wear, not breathable even, preventing the wearer from working for extended hours. Hence, a strong need exists to select and/or create selectively permeable layered fibrous structures with bioactive agents that offer an efficient filtering capability and biocidal skills, ensuring lightweightness, comfort, and multifunctionality. This review aims to showcase the main possibilities and trends of bioprotective textiles, focusing on metal–organic frameworks (MOFs), inorganic nanoparticles (e.g., ZnO-based), and organic players such as chitosan (CS)-based small-scale particles and plant-derived compounds as bioactive agents. The textile itself should be further evaluated as the foundation for the barrier effect and in terms of comfort. The outputs of a thorough, standardized characterization should dictate the best elements for each approach.

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Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies

Cui,

Yang,

Sun

et al. 2024

International Journal of Biological Macromolecules

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Crystal structure of UDP-glucose pyrophosphorylase fromYersinia pestis, a potential therapeutic target against plague

Cited by 6 publications

References 50 publications

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors

Recent Trends in Protective Textiles against Biological Threats: A Focus on Biological Warfare Agents

Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies

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