Range of activity and metabolic stability of synthetic antibacterial glycopeptides from insects

Hoffmann, Ralf; Bulet, Philippe; Ürge, László; Ötvös, László

doi:10.1016/s0304-4165(98)00169-x

Cited by 67 publications

(87 citation statements)

References 25 publications

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“…This is in agreement with previous reports showing that glycosylated forms of drosocin and formaecin are slightly more active than the unglycosylated analogs (Ref. 31, and for reviews, see Refs. 26 and 32).…”

Section: Time Course Of Induction and Quantification Of Mpac-the Levesupporting

confidence: 94%

Primary Structure and in Vitro Antibacterial Properties of the Drosophila melanogaster Attacin C Pro-domain

Rabel

Charlet

Ehret‐Sabatier

et al. 2004

Journal of Biological Chemistry

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In Drosophila melanogaster, seven distinct families of antimicrobial peptides with different structures and specificities are synthesized by the fat body and released into the hemolymph during the immune response. Using microscale high performance liquid chromatography, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and Edman degradation, we have isolated and characterized from immune-challenged Drosophila two novel induced molecules, under the control of the Imd pathway, that correspond to post-translationally modified antimicrobial peptides or peptide fragments. The first molecule is a doubly glycosylated form of drosocin, an O-glycosylated peptide that kills Gram-negative organisms. The second molecule represents a truncated form of the pro-domain of the Drosophila attacin C carrying two post-translational modifications and has significant structural similarities to proline-rich antibacterial peptides including drosocin. We have synthesized this peptide and found that it is active against Gram-negative bacteria. Furthermore, this activity is potentiated when the peptide is used in combination with the Drosophila antimicrobial peptide cecropin A. The synergistic action observed between these two molecules suggests that the truncated post-translationally modified pro-domain of attacin C by itself may play an important role in the antimicrobial defense of Drosophila.

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Section: Time Course Of Induction and Quantification Of Mpac-the Levesupporting

confidence: 94%

Primary Structure and in Vitro Antibacterial Properties of the Drosophila melanogaster Attacin C Pro-domain

Rabel

Charlet

Ehret‐Sabatier

et al. 2004

Journal of Biological Chemistry

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“…Serum and Trypsin Stability-The stability of stomoxyn (12 M final concentration) in the presence of 25% bovine serum was tested according to the procedure described previously (29) except that the stability was evaluated by MALDI-TOF MS. For the trypsin stability study, stomoxyn (0.5 mM in a final volume of 20 l) was incubated with bovine trypsin (Roche Molecular Biochemicals) at an enzyme/peptide ratio of 1/10, according to the manufacturer's directions. At different time points (5,15,30,60, 150 min, and overnight), an aliquot (0.5 l) of the sample was removed, and the reaction was stopped with trifluoroacetic acid.…”

Section: Bioassaysmentioning

confidence: 99%

Epithelial Innate Immunity

Boulanger¹,

Munks²,

Hamilton³

et al. 2002

Journal of Biological Chemistry

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The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and nagana.Epithelial intestinal innate immunity plays a major role in the control of infectious diseases in vertebrates (1, 2). In invertebrates, data are still fragmentary despite gut epithelium being an essential interface for parasites during their development in insect vectors. Understanding vector biology is a key element in the control of many parasitic diseases. In this context, the comparison of the trypanosome vector Glossina with the sympatric but non-vector Stomoxys calcitrans is particularly interesting. The tsetse fly Glossina spp. is the major vector of the range of trypanosomes that cause African sleeping sickness in humans and nagana in livestock. Stable flies, Stomoxys spp., feed on the same vertebrate hosts as tsetse flies and have a very similar digestive physiology and midgut anatomy. Although Stomoxys is constantly exposed to trypanosomes, it kills them in the midgut within 2-4 days of ingestion (3). So Stomoxys is not a cyclical vector of trypanosomes (although it can act as a mechanical vector, "flying pin"). Why Stomoxys is not a cyclical vector of trypanosomes is unknown. Recent studies have shown that the insect immune system plays a determinant role in the fate of trypanosome infections in tsetse flies (4, 5). Consequently, in this report, we address the possibility that the distinction in vectorial capacity between Glossina and Stomoxys may lie in differences in immune mechanisms.Trypanosoma vivax matures entirely in the mouthparts of Glossina. The other trypanosomes causing nagana and human disease are ingested into the fly midgut where they multiply first in the endoperitrophic space and later in the ectoperitrophic space tightly sandwiched between the peritrophic matrix and the ...

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“…Their importance gained widespread recognition in 2011, when Jules Hoffmann received the Nobel Prize in physiology or medicine for his pioneering work on innate immunity mechanisms, including identification of AMP from insects and discovery of the genetic background of their synthesis [8]. Unfortunately neither native drosocin [9] nor pyrrhocoricin [10] that the Hoffmann group isolated from insects after pricking them with Escherichia coli shows efficacy against experimental E. coli infection in higher animals, such as mice [11]. Thus, it must be something else than direct killing of microbes that make mammalianderived peptides active and insect-derived peptides inactive in animal models of bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects of anti-microbial peptides

Ötvös¹

2016

Acta Microbiologica et Immunologica Hungarica

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Anti-microbial peptides (AMPs) were originally thought to exert protecting actions against bacterial infection by disintegrating bacterial membranes. Upon identification of internal bacterial targets, the view changed and moved toward inhibition of prokaryote-specific biochemical processes. However, the level of none of these activities can explain the robust efficacy of some of these peptides in animal models of systemic and cutaneous infections. A rapidly growing panel of reports suggests that AMPs, now called host-defense peptides (HDPs), act through activating the immune system of the host. This includes recruitment and activation of macrophages and mast cells, inducing chemokine production and altering NF-κB signaling processes. As a result, both pro-and anti-inflammatory responses are elevated together with activation of innate and adaptive immunity mechanisms, wound healing, and apoptosis. HDPs sterilize the systemic circulation and local injury sites significantly more efficiently than pure single-endpoint in vitro microbiological or biochemical data would suggest and actively aid recovering from tissue damage after or even without bacterial infections. However, the multiple and, often opposing, immunomodulatory functions of HDPs require exceptional care in therapeutic considerations.

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Range of activity and metabolic stability of synthetic antibacterial glycopeptides from insects

Cited by 67 publications

References 25 publications

Primary Structure and in Vitro Antibacterial Properties of the Drosophila melanogaster Attacin C Pro-domain

Primary Structure and in Vitro Antibacterial Properties of the Drosophila melanogaster Attacin C Pro-domain

Epithelial Innate Immunity

Immunomodulatory effects of anti-microbial peptides

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