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Beta-defensin derived cationic antimicrobial peptides with potent killing activity against gram negative and gram positive bacteria

Overview of attention for article published in BMC Microbiology, June 2018
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Title
Beta-defensin derived cationic antimicrobial peptides with potent killing activity against gram negative and gram positive bacteria
Published in
BMC Microbiology, June 2018
DOI 10.1186/s12866-018-1190-z
Pubmed ID
Authors

Ming Yang, Chunye Zhang, Michael Z. Zhang, Shuping Zhang

Abstract

Avian β-defensins (AvBD) are cationic antimicrobial peptides (CAMP) with broad-spectrum antimicrobial activity, chemotactic property, and low host cytotoxicity. However, their bactericidal activity is greatly compromised under physiological salt concentrations which limits the use of these peptides as therapeutic agents. The length and the complex structure involving three conserved disulfide bridges are additional drawbacks associated with high production cost. In the present study, short linear CAMPs (11 to 25 a.a. residues) were developed based on the key functional components of AvBDs with additional modifications. Their biological functions were characterized. CAMP-t1 contained the CCR2 binding domain (N-terminal loop and adjacent α-helix) of AvBD-12 whereas CAMP-t2 comprised the key a.a. residues responsible for the concentrated positive surface charge and hydrophobicity of AvBD-6. Both CAMP-t1 and CAMP-t2 demonstrated strong antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus pseudintermedius. However, CAMP-t1 failed to show chemotactic activity and CAMP-t2, although superior in killing Staphylococcus spp., remained sensitive to salts. Using an integrated design approach, CAMP-t2 was further modified to yield CAMP-A and CAMP-B which possessed the following characteristics: α-helical structure with positively and negatively charged residues aligned on the opposite side of the helix, lack of protease cutting sites, C-terminal poly-Trp tail, N-terminal acetylation, and C-terminal amidation. Both CAMP-A and CAMP-B demonstrated strong antimicrobial activity against multidrug-resistant P. aeruginosa and methicillin-resistant S. pseudintermedius (MRSP) strains. These peptides were resistant to major proteases and fully active at physiological concentrations of NaCl and CaCl2. The peptides were minimally cytotoxic to avian and murine cells and their therapeutic index was moderate (≥ 4.5). An integrated design approach can be used to develop short and potent antimicrobial peptides, such as CAMP-A and CAMP-B. The advantageous characteristics, including structural simplicity, resistance to salts and proteases, potent antimicrobial activity, rapid membrane attacking mode, and moderate therapeutic index, suggest that CAMP-A and CAMP-B are excellent candidates for development as therapeutic agents against multidrug-resistant P. aeruginosa and methicillin-resistant staphylococci.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 24%
Researcher 7 11%
Student > Bachelor 5 8%
Student > Master 4 6%
Student > Doctoral Student 3 5%
Other 10 16%
Unknown 19 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 16%
Agricultural and Biological Sciences 9 14%
Immunology and Microbiology 6 10%
Medicine and Dentistry 4 6%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 9 14%
Unknown 23 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 08 June 2018.
All research outputs
#18,637,483
of 23,088,369 outputs
Outputs from BMC Microbiology
#2,264
of 3,216 outputs
Outputs of similar age
#254,906
of 329,782 outputs
Outputs of similar age from BMC Microbiology
#21
of 37 outputs
Altmetric has tracked 23,088,369 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,216 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 15th percentile – i.e., 15% of its peers scored the same or lower than it.
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 329,782 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one is in the 21st percentile – i.e., 21% of its contemporaries scored the same or lower than it.