Synthesis of Protegrin-Related Peptides and Their Antibacterial and Anti-human Immunodeficiency Virus Activity.

Tamamura, Hirokazu; Murakami, Tsutomu; Horiuchi, Sankichi; Sugihara, K.; Otaka, Akira; Takada, Wataru; Ibuka, Toshiro; Waki, Michinori; Yamamoto, Naoki; Fujii, Nobutaka

doi:10.1248/cpb.43.853

Cited by 95 publications

(69 citation statements)

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“…Among five known congeners, protegrins 1-3 have been purified from porcine PMNs [61], and the other two, protegrins 4-5, were derived from a bone marrow cDNA and a gene sequence, respectively [136,137]. Protegrins exhibit potent, broadspectrum, microbicidal activity against various gram-positive and -negative bacteria, mycobacteria, fungi, and enveloped viruses, including several sexually transmitted human pathogens, Chlamydia trachomatis, Neisseria gonorrhoeae, and Haemophilus ducreyi; periodontopathic bacteria, Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum; and HIV type I virions [23,79,80,91,115].…”

Section: Protegrins a Group Of Compactmentioning

confidence: 99%

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Zhang¹,

Ross²,

Blecha³

2000

Vet. Res.

111

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-Antimicrobial peptides (AMPs) are small, endogenous, polycationic molecules that constitute a ubiquitous and significant component of innate immunity. These natural antibiotics have broad microbicidal activity against various bacteria, fungi, and enveloped viruses. Because most AMPs kill bacteria by physical disruption of cell membranes, which may prevent microorganisms from developing resistance against these agents, they are being explored as possible alternatives to conventional antibiotics. Pigs, like many other mammals, produce an impressive array of AMPs, which are synthesized predominantly by host leukocytic phagocytes or mucosal epithelial cells. Currently, more than a dozen distinct porcine AMPs have been identified and a majority belongs to the cathelicidin family. This review briefly summarizes recent advances in porcine AMP research with an emphasis on the diverse biological functions of each peptide. Mechanisms of action of these AMPs and their role in the resistance to infections are considered. Finally, the current status of pharmaceutical and agricultural uses of AMPs as well as future prospects for their application in the food animal industry is discussed.pig / antimicrobial peptide / cathelicidin / defensin / innate immunity Résumé -Peptides antimicrobiens porcins : nouvelles perspectives pour d'anciennes molécules de défense de l'hôte. Les peptides antimicrobiens sont de petites molécules endogènes, polycationiques, qui représentent un élément important et ubiquitaire des défenses immunes naturelles. Ces antibiotiques naturels ont un effet antimicrobien à large spectre, à la fois contre des bactéries, des moisissures et des virus enveloppés. Comme la plupart de ces peptides antimicrobiens tuent les bactéries par altération physique de leur membrane, ce qui peut éviter le développement de souches microbiennes résistantes à ces agents, ils représentent des alternatives possibles à l'emploi des antibiotiques classiques. Le porc, comme de nombreux autres mammifères, produit une gamme importante de peptides antimicrobiens, synthétisés pour l'essentiel par les leucocytes à activité phagocytaire, ou par les cellules épithéliales des muqueuses. Il y a actuellement plus d'une douzaine de peptides antimicrobiens identifiés chez le porc, dont la majorité fait partie de la famille des cathélicidines. Cet article résume les progrès récents accomplis dans le domaine des peptides antimicrobiens du porc, Vet. Res. 31 (2000) 277-296 277

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Section: Protegrins a Group Of Compactmentioning

confidence: 99%

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Zhang¹,

Ross²,

Blecha³

2000

Vet. Res.

111

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“…In humans, cathelicidins have also been found to be expressed in several other tissues, including the testis (Agerberth et al 1995;Malm et al 2000), squamous epithelia (Frohm Nilsson et al 1999;Nizet et al 2001), airway epithelia (Bals et al 1998), sweat glands (Murakami et al 2002b), salivary glands (Murakami et al 2002a) and colon (Hase et al 2002). Cathelicidins have a wide spectrum of antimicrobial activity and have been shown to be active against Gram-negative and Grampositive bacteria (Travis et al 2000), fungi (Shin et al 2000) and enveloped viruses (Tamamura et al 1995). Activity against a particular microbe depends on the type of mature peptide and the species from which it originates.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic discovery and initial characterisation of nine novel antimicrobial peptide genes in the chicken

et al. 2004

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Antimicrobial peptides (AMPs) are essential components of innate immunity in a range of species fromDrosophila to humans and are generally thought to act by disrupting the membrane integrity of microbes. In order to discover novel AMPs in the chicken, we have implemented a bioinformatic approach that involves the clustering of more than 420,000 chicken expressed sequence tags (ESTs). Similarity searching of proteinspredicted to be encoded by these EST clusters-for homology to known AMPs has resulted in the in silico identification of full-length sequences for seven novel gallinacins (Gal-4 to Gal-10), a novel cathelicidin and a novel liver-expressed antimicrobial peptide 2 (LEAP-2) in the chicken. Differential gene expression of these novel genes has been demonstrated across a panel of chicken tissues. An evolutionary analysis of the gallinacin family has detected sites-primarily in the mature AMP-that are under positive selection in these molecules. The functional implications of these results are discussed.

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“…To minimize the development of antibiotic resistance and to retain consumer confidence in food safety, alternative approaches of controlling infection in animal production are needed. Protegrin-1 (PG-1), one of the most potent antimicrobial peptides (1,11,39), targets both gram-negative and grampositive bacteria, including bacteria that demonstrate in vivo antibiotic resistance (11,21,27,32,34). In addition, it has been shown to reduce lentiviral infectivity and to have activity against enveloped viruses, including human immunodeficiency virus (33,34).…”

mentioning

confidence: 99%

Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

Cheung¹,

Turner²,

Song³

et al. 2008

Antimicrob Agents Chemother

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Antibiotic-resistant bacteria have become a public health concern. It was suggested that one source of resistant pathogens may be food-producing animals. Alternative approaches are therefore needed to enhance the resistance of farm animals to bacterial infection. Protegrin-1 (PG-1) is a neutrophil-derived antimicrobial peptide that possesses activity against a wide range of bacteria and enveloped viruses. Here we report on the production of transgenic mice that ectopically expressed PG-1 and compare their susceptibilities to Actinobacillus suis infection with those of their wild-type (WT) littermates. Of the 126 mice that were challenged with A. suis, 87% of the transgenic mice survived, whereas 31% of their WT littermates survived. The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. The antimicrobial function of PG-1 was confirmed in vitro by using fibroblast cells isolated from the transgenic mice but not the WT mice. Moreover, differential blood cell counts in bronchoalveolar lavage fluid indicated greater number of neutrophils in PG-1 transgenic mice than in their WT littermates after bacterial challenge. Our data suggest that the ectopic expression of PG-1 in mice confers enhanced resistance to bacterial infection, laying the foundation for the development of livestock with improved resistance to infection.

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Synthesis of Protegrin-Related Peptides and Their Antibacterial and Anti-human Immunodeficiency Virus Activity.

Cited by 95 publications

References 0 publications

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Bioinformatic discovery and initial characterisation of nine novel antimicrobial peptide genes in the chicken

Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

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