In vitro and in vivo Evaluation of in silico Predicted Pneumococcal UDPG:PP Inhibitors
Frontiers in Microbiology, ISSN: 1664-302X, Vol: 11, Page: 1596
2020
- 6Citations
- 23Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations6
- Citation Indexes6
- Captures23
- Readers23
- 23
Article Description
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.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85088979329&origin=inward; http://dx.doi.org/10.3389/fmicb.2020.01596; http://www.ncbi.nlm.nih.gov/pubmed/32760374; https://www.frontiersin.org/articles/10.3389/fmicb.2020.01596/supplementary-material/10.3389/fmicb.2020.01596.s001; http://dx.doi.org/10.3389/fmicb.2020.01596.s001; https://www.frontiersin.org/article/10.3389/fmicb.2020.01596/full; https://dx.doi.org/10.3389/fmicb.2020.01596; https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01596/full; https://dx.doi.org/10.3389/fmicb.2020.01596.s001
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