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High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as Novel Alternatives to Antibiotics

Overview of attention for article published in Frontiers in Cellular and Infection Microbiology, June 2018
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  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

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Title
High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as Novel Alternatives to Antibiotics
Published in
Frontiers in Cellular and Infection Microbiology, June 2018
DOI 10.3389/fcimb.2018.00191
Pubmed ID
Authors

Wentao Lyu, Zhuo Deng, Lakshmi T. Sunkara, Sage Becker, Kelsy Robinson, Robert Matts, Guolong Zhang

Abstract

A rise in antimicrobial resistance demands novel alternatives to antimicrobials for disease control and prevention. As an important component of innate immunity, host defense peptides (HDPs) are capable of killing a broad spectrum of pathogens and modulating a range of host immune responses. Enhancing the synthesis of endogenous HDPs has emerged as a novel host-directed antimicrobial therapeutic strategy. To facilitate the identification of natural products with a strong capacity to induce HDP synthesis, a stable macrophage cell line expressing a luciferase reporter gene driven by a 2-Kb avian β-defensin 9 (AvBD9) gene promoter was constructed through lentiviral transduction and puromycin selection. A high throughput screening assay was subsequently developed using the stable reporter cell line to screen a library of 584 natural products. A total of 21 compounds with a minimum Z-score of 2.0 were identified. Secondary screening in chicken HTC macrophages and jejunal explants further validated most compounds with a potent HDP-inducing activity in a dose-dependent manner. A follow-up oral administration of a lead natural compound, wortmannin, confirmed its capacity to enhance the AvBD9 gene expression in the duodenum of chickens. Besides AvBD9, most other chicken HDP genes were also induced by wortmannin. Additionally, butyrate was also found to synergize with wortmannin and several other newly-identified compounds in AvBD9 induction in HTC cells. Furthermore, wortmannin acted synergistically with butyrate in augmenting the antibacterial activity of chicken monocytes. Therefore, these natural HDP-inducing products may have the potential to be developed individually or in combinations as novel antibiotic alternatives for disease control and prevention in poultry and possibly other animal species including humans.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 17%
Other 5 14%
Student > Bachelor 3 8%
Student > Master 3 8%
Student > Ph. D. Student 3 8%
Other 6 17%
Unknown 10 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 19%
Agricultural and Biological Sciences 6 17%
Veterinary Science and Veterinary Medicine 2 6%
Social Sciences 2 6%
Immunology and Microbiology 2 6%
Other 5 14%
Unknown 12 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 June 2018.
All research outputs
#13,866,924
of 23,508,125 outputs
Outputs from Frontiers in Cellular and Infection Microbiology
#2,358
of 6,824 outputs
Outputs of similar age
#170,893
of 329,259 outputs
Outputs of similar age from Frontiers in Cellular and Infection Microbiology
#52
of 122 outputs
Altmetric has tracked 23,508,125 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,824 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,259 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 122 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.