Discovery of five conserved β-defensin gene clusters using a computational search strategy

Schutte, Brian C.; Mitros, Joseph; Bartlett, Jennifer; Walters, Jesse D.; Jia, Hong Peng; Welsh, Michael J.; Casavant, Thomas L.; McCray, Paul B.

doi:10.1073/pnas.042692699

Cited by 461 publications

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“…1 In humans more than 30 b-defensins are organized in five syntenic chromosomal regions. 2 Two of these functional human defensin gene clusters were previously investigated. 3,4 Human b-defensins (DEFB) are expressed by epithelial cells lining tissues facing the external environment.…”

Section: Introductionmentioning

confidence: 99%

Identification, characterization, and evolution of a primate β-defensin gene cluster

et al. 2005

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Defensins are members of a large diverse family of cationic antimicrobial peptides that share a signature pattern consisting of six conserved cysteine residues. Defensins have a wide variety of functions and their disruption has been implicated in various human diseases. Here we report the characterization of DEFB119-DEFB123, five genes in the human b-defensin cluster locus on chromosome 20q11.1. The genomic structures of DEFB121 and DEFB122 were determined in silico. Sequences of the five macaque orthologs were obtained and expression patterns of the genes were analyzed in humans and macaque by semiquantitative reverse transcription polymerase chain reaction. Expression was restricted to the male reproductive tract. The genes in this cluster are differentially regulated by androgens. Evolutionary analyses suggest that this cluster originated by a series of duplication events and by positive selection. The evolutionary forces driving the proliferation and diversification of these defensins may be related to reproductive specialization and/or the host-parasite coevolutionary process.

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Section: Introductionmentioning

confidence: 99%

Identification, characterization, and evolution of a primate β-defensin gene cluster

et al. 2005

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“…Antimicrobial activity of beta-defensins can be decreased by high salt concentrations [4,7 -9]; however, recent studies indicate that osmotic agents such as xylitol may enhance defensin activity, even in high salt conditions [10]. Over 26 human beta-defensins have been identified [11,12]. Expression of some beta-defensins, such as human beta-defensin-1 (HBD-1), is constitutive, whereas expression of other beta-defensins, such as HBD-2, 3, and 4, [4,8,13], mouse beta-defensin-2 [14], tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) of cattle, is inducible [15 -18].…”

Section: Introductionmentioning

confidence: 99%

Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia

Ackermann¹,

Gallup²,

Zabner³

et al. 2004

Microbial Pathogenesis

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Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Coinoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AuthorsMark R. Ackermann, Jack M. Abstract Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, b...

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“…3 Based on their size and the spatial position of the six cysteine residues, animal defensins are classified as a-, b-, y-defensins of vertebrates (mammalia and birds) and insect defensins. To date, vertebrate defensins were identified in numerous species: mice, [6][7][8] birds-where they are called gallinacins- 9 rats, 10 cattle, 11,12 goats, 13 sheeps, 14 humans, 8,15,16 and non-human primates [17][18][19][20] (reviewed in Martin et al, 4 Hughes, 21 Schroder, 22 and Lehrer and Ganz 23 ). Interestingly, domestic cattle (Bos taurus) was shown to share a broad spectrum of different b-defensins, for example, tap (tracheal antimicrobial peptide), lap (lingual antimicrobial peptide), bnbd (bovine neutrophil peptide), nbd12 (neutrophil beta defensin 12), and ebd (enteric beta defensin).…”

Section: Introductionmentioning

confidence: 99%

Variability and evolution of bovine β-defensin genes

Luenser

Ludwig

2004

Genes Immun

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Defensins comprise an important family of antimicrobial peptides. Among vertebrates numerous defensin genes have been detected, but their evolutionary background is still discussed. We investigated the molecular evolution of bovine defensins via screening of different bovine species including the extinct ancestor of domestic cattle (Bos primigenius) for b-defensin encoding genes. We detected a large variability of new defensin encoding sequences similar to previously published bovine neutrophil b-defensin (bnbd), neutrophil b-defensin 12 (nbd12), enteric b-defensin (ebd), lingual antimicrobial peptide (lap), and tracheal antimicrobial peptide (tap). Our data suggest that variants of the same so-called subfamily (tap, lap, ebd, and nbd12) each share a common ancestry independent of their species origin, implicating several duplication events of tap, lap, ebd, and nbd12 before the different bovine lineages diverged. Variants of bovine neutrophil b-defensins bnbd5 and bnbd9 were detected exclusively in domestic cattle and aurochs. Values of synonymous and nonsynonymous substitutions demonstrated lap, bnbd5, bnbd9 and nbd12 evolving under positive selection, whereas amino-acid altering substitutions among variants of ebd and tap are purified. Comparison of the amino-acid sequences with available structures of human and murine defensins suggested conservation of the typical secondary elements of defensins in the absence of high sequence similarity.

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Discovery of five conserved β-defensin gene clusters using a computational search strategy

Abstract: Corrections GENETICS.As an addendum for the article ''Discovery of five conserved ␤-defensin gene clusters using a computational search strategy,''

Cited by 461 publications

References 33 publications

Identification, characterization, and evolution of a primate β-defensin gene cluster

Identification, characterization, and evolution of a primate β-defensin gene cluster

Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia

Variability and evolution of bovine β-defensin genes

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