Abstract: Defensins represent an important class of antimicrobial peptides. These effector molecules of the innate immune system act as endogenous antibiotics to protect the organism against infections with pathogenic microorganisms. Mammalian defensins are classified into three distinct sub-families (alpha-, beta- and theta-defensins) according to their specific intramolecular disulfide-bond pattern. The peptides exhibit an antimicrobial activity against a broad spectrum of microorganisms including bacteria and fungi. Alpha-Defensins are primarily synthesised in neutrophils and intestinal Paneth cells. They play a role in the pathogenesis of intestinal diseases and may regulate the flora of the intestinal tract. An equine intestinal alpha-defensin (DEFA1), the first characterised in the Laurasiatheria, shows a broad antimicrobial spectrum against human and equine pathogens. Here we report a first investigation of the repertoire of equine intestinal alpha-defensins. The equine genome was screened for putative alpha-defensin genes by using known alpha-defensin sequences as matrices. Based on the obtained sequence information, a set of oligonucleotides specific to the alpha-defensin gene-family was designed. The products generated by reverse-transcriptase PCR with cDNA from the small intestine as template were sub-cloned and numerous clones were sequenced. Results: Thirty-eight equine intestinal alpha-defensin transcripts were determined. After translation it became evident that at least 20 of them may code for functional peptides. Ten transcripts lacked matching genomic sequences and for 14 alpha-defensin genes apparently present in the genome no appropriate transcript could be verified. In other cases the same genomic exons were found in different transcripts. Conclusions: The large repertoire of equine alpha-defensins found in this study points to a particular importance of these peptides regarding animal health and protection from infectious diseases. Moreover, these findings make the horse an excellent species to study biological properties of alpha-defensins. Interestingly, the peptides were not found in other species of the Laurasiatheria to date. Comparison of the obtained transcripts with the genomic sequences in the current assembly of the horse (EquCab2.0) indicates that it is yet not complete and/or to some extent falsely assembled.
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article studies the classification and function of defensins, focusing specifically on alpha-defensins found in the equine intestinal tract. The study analysed the equine genome to understand the diverse range of these peptides and discovered a broad antimicrobial spectrum effective against various pathogens.
Understanding Defensins
Defensins are a type of antimicrobial peptide, which acts as an innate antibiotic, providing protection against various microorganisms.
Mammalian defensins are put into three sub-categories – alpha-, beta-, and theta-defensins, classified through their specific disulfide-bond pattern.
These peptides display antimicrobial action against a wide range of microorganisms, including dangerous bacteria and fungi.
Role of Alpha-Defensins in Equine Intestinal System
Alpha-Defensins are found primarily in neutrophils and intestinal Paneth cells and play a key role in the development of intestinal diseases. They might also regulate the flora present in the intestinal tract.
The research specifically focuses on an equine intestinal alpha-defensin (DEFA1). This defensin exhibits a broad antimicrobial spectrum useful against both human and equine pathogens.
Studying the Equine Intestinal Alpha-Defensins
The study involved screening the equine genome for possible alpha-defensin genes using existing alpha-defensin sequences as references.
The collected sequence information was used to design a set of oligonucleotides specific to the alpha-defensin gene-family for further investigation.
Results and Conclusions
The analysis of the equine genome identified thirty-eight equine intestinal alpha-defensin transcripts.
Among these, at least 20 might code for functional peptides, while ten transcripts showed no matching genomic sequences.
Of the 14 alpha-defensin genes apparently present in the genome, no appropriate transcript could be verified.
Several cases showed that identical genomic exons were found in different transcripts.
The researchers concluded that the substantial repertory of equine alpha-defensins suggests their critical importance to animal health and guarding against infectious diseases.
The results indicate that horses could serve as an ideal species for studying the biological properties of alpha-defensins.
This study further sheds light on incomplete or incorrect assembly in the current version of the horse genome (EquCab2.0).
Cite This Article
APA
Bruhn O, Paul S, Tetens J, Thaller G.
(2009).
The repertoire of equine intestinal alpha-defensins.
BMC Genomics, 10, 631.
https://doi.org/10.1186/1471-2164-10-631
Institute of Animal Breeding and Husbandry, Christian-Albrechts-University of Kiel, Hermann-Rodewald-Strasse 6, D-24118 Kiel, Germany. obruhn@tierzucht.uni-kiel.de
Paul, Sven
Tetens, Jens
Thaller, Georg
MeSH Terms
Amino Acid Sequence
Animals
DNA, Complementary / genetics
Genome
Horses / genetics
Intestine, Small / metabolism
Molecular Sequence Data
Multigene Family
Sequence Alignment
Sequence Analysis, DNA
alpha-Defensins / genetics
References
This article includes 49 references
Zasloff M. Antimicrobial peptides of multicellular organisms.. Nature 2002 Jan 24;415(6870):389-95.
Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, Selsted ME. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity.. J Clin Invest 1989 Aug;84(2):553-61.
Sitaram N, Nagaraj R. Interaction of antimicrobial peptides with biological and model membranes: structural and charge requirements for activity.. Biochim Biophys Acta 1999 Dec 15;1462(1-2):29-54.
Tang YQ, Yuan J, Miller CJ, Selsted ME. Isolation, characterization, cDNA cloning, and antimicrobial properties of two distinct subfamilies of alpha-defensins from rhesus macaque leukocytes.. Infect Immun 1999 Nov;67(11):6139-44.
Yount NY, Wang MS, Yuan J, Banaiee N, Ouellette AJ, Selsted ME. Rat neutrophil defensins. Precursor structures and expression during neutrophilic myelopoiesis.. J Immunol 1995 Nov 1;155(9):4476-84.
Sinha S, Cheshenko N, Lehrer RI, Herold BC. NP-1, a rabbit alpha-defensin, prevents the entry and intercellular spread of herpes simplex virus type 2.. Antimicrob Agents Chemother 2003 Feb;47(2):494-500.
Belov K, Sanderson CE, Deakin JE, Wong ES, Assange D, McColl KA, Gout A, de Bono B, Barrow AD, Speed TP, Trowsdale J, Papenfuss AT. Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system.. Genome Res 2007 Jul;17(7):982-91.
Fjell CD, Jenssen H, Fries P, Aich P, Griebel P, Hilpert K, Hancock RE, Cherkasov A. Identification of novel host defense peptides and the absence of alpha-defensins in the bovine genome.. Proteins 2008 Nov 1;73(2):420-30.
Patil A, Hughes AL, Zhang G. Rapid evolution and diversification of mammalian alpha-defensins as revealed by comparative analysis of rodent and primate genes.. Physiol Genomics 2004 Dec 15;20(1):1-11.
Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria.. Nat Immunol 2000 Aug;1(2):113-8.
Wehkamp J, Salzman NH, Porter E, Nuding S, Weichenthal M, Petras RE, Shen B, Schaeffeler E, Schwab M, Linzmeier R, Feathers RW, Chu H, Lima H Jr, Fellermann K, Ganz T, Stange EF, Bevins CL. Reduced Paneth cell alpha-defensins in ileal Crohn's disease.. Proc Natl Acad Sci U S A 2005 Dec 13;102(50):18129-34.
Ferguson LR, Browning BL, Huebner C, Petermann I, Shelling AN, Demmers P, McCulloch A, Gearry RB, Barclay ML, Philpott M. Single nucleotide polymorphisms in human Paneth cell defensin A5 may confer susceptibility to inflammatory bowel disease in a New Zealand Caucasian population.. Dig Liver Dis 2008 Sep;40(9):723-30.
Kelly P, Bajaj-Elliott M, Katubulushi M, Zulu I, Poulsom R, Feldman RA, Bevins CL, Dhaliwal W. Reduced gene expression of intestinal alpha-defensins predicts diarrhea in a cohort of African adults.. J Infect Dis 2006 May 15;193(10):1464-70.
Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symposium Series 1999;41:95–98.
Wu Z, Li X, de Leeuw E, Ericksen B, Lu W. Why is the Arg5-Glu13 salt bridge conserved in mammalian alpha-defensins?. J Biol Chem 2005 Dec 30;280(52):43039-47.
Xie C, Prahl A, Ericksen B, Wu Z, Zeng P, Li X, Lu WY, Lubkowski J, Lu W. Reconstruction of the conserved beta-bulge in mammalian defensins using D-amino acids.. J Biol Chem 2005 Sep 23;280(38):32921-9.
Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins.. Antimicrob Agents Chemother 2005 Jan;49(1):269-75.
Inoue R, Tsuruta T, Nojima I, Nakayama K, Tsukahara T, Yajima T. Postnatal changes in the expression of genes for cryptdins 1-6 and the role of luminal bacteria in cryptdin gene expression in mouse small intestine.. FEMS Immunol Med Microbiol 2008 Apr;52(3):407-16.
Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, Springer MS. Resolution of the early placental mammal radiation using Bayesian phylogenetics.. Science 2001 Dec 14;294(5550):2348-51.
Whittington CM, Papenfuss AT, Bansal P, Torres AM, Wong ES, Deakin JE, Graves T, Alsop A, Schatzkamer K, Kremitzki C, Ponting CP, Temple-Smith P, Warren WC, Kuchel PW, Belov K. Defensins and the convergent evolution of platypus and reptile venom genes.. Genome Res 2008 Jun;18(6):986-94.
Aldred PM, Hollox EJ, Armour JA. Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3.. Hum Mol Genet 2005 Jul 15;14(14):2045-52.
Tang YQ, Yuan J, Osapay G, Osapay K, Tran D, Miller CJ, Ouellette AJ, Selsted ME. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins.. Science 1999 Oct 15;286(5439):498-502.
Shamova O, Brogden KA, Zhao C, Nguyen T, Kokryakov VN, Lehrer RI. Purification and properties of proline-rich antimicrobial peptides from sheep and goat leukocytes.. Infect Immun 1999 Aug;67(8):4106-11.
Jones S, Spier SJ. Inflammatory diseases of the large intestine causing diarrhea. Equine Internal Medicine Philadelphia: W. B. Saunders Company; 1998; pp. 663–682.
Murray MJ. Duodenitis-proximal jejunitis. Equine Internal Medicine Philadelphia: W. B. Saunders Company; 1998; pp. 623–627.
Dong H, Dong Z, Wang F, Wang G, Luo X, Lei C, Chen J. Whole Genome Sequencing Provides New Insights Into the Genetic Diversity and Coat Color of Asiatic Wild Ass and Its Hybrids. Front Genet 2022;13:818420.
Wang M, Zhou Z, Li S, Zhu W, Hu X. Identification and Characterization of Antimicrobial Peptides From Butterflies: An Integrated Bioinformatics and Experimental Study. Front Microbiol 2021;12:720381.
Kumar R, Ali SA, Singh SK, Bhushan V, Mathur M, Jamwal S, Mohanty AK, Kaushik JK, Kumar S. Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects. Vet Sci 2020 Dec 18;7(4).
Hall TJ, McQuillan C, Finlay EK, O'Farrelly C, Fair S, Meade KG. Comparative genomic identification and validation of β-defensin genes in the Ovis aries genome. BMC Genomics 2017 Apr 4;18(1):278.
Lan H, Chen H, Chen LC, Wang BB, Sun L, Ma MY, Fang SG, Wan QH. The first report of a Pelecaniformes defensin cluster: characterization of β-defensin genes in the crested ibis based on BAC libraries. Sci Rep 2014 Nov 5;4:6923.