Identification of novel host defense peptides and the absence of α-defensins in the bovine genome

被引:48
|
作者
Fjell, Christopher D. [1 ]
Jenssen, Havard [2 ]
Fries, Patrick [3 ]
Aich, Palok [3 ]
Griebel, Philip [3 ]
Hilpert, Kai [2 ]
Hancock, Robert E. W. [2 ]
Cherkasov, Artem [1 ]
机构
[1] Univ British Columbia, Div Infect Dis, Dept Med, Fac Med, Vancouver, BC V5Z 3J5, Canada
[2] Univ British Columbia, Ctr Microbiol Dis & Immun Res, Vancouver, BC V5Z 3J5, Canada
[3] Univ Saskatchewan, Vaccine & Infect Dis Org, Saskatoon, SK, Canada
关键词
antimicrobial peptides; AMPer; hidden Markov models; innate immune system;
D O I
10.1002/prot.22059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Host defense peptides (historically called antimicrobial peptides, AMPs) are key components in the mammalian innate immune system, and are responsible for both direct killing and immunomodulatory effects in host defense against pathogenic organisms. In order to identify novel host defense peptides by sequence analysis, we constructed the AMPer resource (http://www.cnbi2.com/cgi-bin/amp.pl) that utilizes hidden Markov models to recognize sequences of antimicrobial peptides. In the current work, we utilized the AMPer resource to search bovine expressed sequence tags from the NCBI dbEST project and the bovine genome sequence for novel host defense peptides. Of the 34 known bovine AMPs, 27 were identified with high confidence in the AMPs predicted from ESTs. A further potential 68 AMPs predicted from the EST data were found that appear to be novel giving a total estimate of 102 AMPs present in the genome. Two of these were cathelicidins and selected for experimental verification in RNA derived from bovine tissue. One predicted AMP, most similar to rabbit '15 kDa protein' AMP, was confirmed to be present in infected bovine intestinal tissue using PCR. These findings demonstrated the practical applicability of the developed bioinformatics approach and laid a foundation for future discoveries of gene-coded AMPs. No members of the alpha-defensin family were found in the bovine sequences. Since we could find no technical reasons these would be missed and no references to bovine alpha-defensins in the literature, this suggests that cattle lack this important family of host defense peptides.
引用
收藏
页码:420 / 430
页数:11
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