Peptide antimicrobien

Résumé

vignette|350x350px| Différentes structures de peptides antimicrobiens Les peptides antimicrobiens (PAM), (AMPs en anglais) également appelés peptides de défense de l'hôte (HDPs en anglais), font partie de la réponse immunitaire innée trouvée dans toutes les classes de la vie. Des différences fondamentales existent entre les cellules procaryotes et eucaryotes pouvant représenter des cibles pour les peptides antimicrobiens. Ces peptides sont de puissants antibiotiques à large spectre qui présentent un potentiel en tant que nouveaux agents thérapeutiques. Il a été démontré que les peptides antimicrobiens tuent les bactéries à Gram négatif et à Gram positif, les virus enveloppés, les champignons et même les cellules transformées ou cancéreuses. Contrairement à la majorité des antibiotiques classiques, il apparaît que les peptides antimicrobiens déstabilisent fréquemment les membranes biologiques, peuvent former des canaux transmembranaires et peuvent également en jouant le rôle d’ immuno

Source officielle

https://fr.wikipedia.org/wiki/Peptide_antimicrobien

À propos de ce résultat

Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.

Publications associées (100)

Chargement

Afficher plus

Publications associées

Chargement

Personnes associées (7)

Personnes associées

Chargement

Unités associées (2)

Unités associées

Chargement

Concepts associés (22)

Concepts associés

Chargement

Cours associés (12)

Cours associés

Chargement

Séances de cours associées (28)

Séances de cours associées

Chargement

Publications associées (100)

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microbes. These short immune effectors are conserved in plants, animals, and fungi. Early work showed that AMPs killed bacteria in generalist fashions in vitro: i.e. AMPs that killed Escherichia coli also killed many Gram-negative bacteria when tested. At the genome level, AMP gene families rapidly expand or contract, which suggested single genes were unlikely to be important. At the signalling level, AMPs are induced as a suite of peptides by conserved NF-ÎºB immune pathways across organisms (e.g. Toll, Imd). Together these observations led to the assump-tion that individual genes contributed only small effects, and instead the cumulative cocktail of AMPs was key to a successful de-fence response. This idea was never robustly tested in vivo owing to technical limitations. In 2015, two studies stumbled onto re-markable effects of fruit fly immune effectors. In one case a polymorphism in a single AMP gene (Diptericin A or DptA) greatly af-fected the fly defence against a specific bacterium (Providencia rettgeri). In another case, deleting just the Bomanin gene family caused immune susceptibility mimicking loss of Toll signalling generally. The prevailing model of generalist AMP action was ill equipped to explain these findings.In my PhD, I have systematically deleted the AMP genes of fruit flies to clarify AMP defences in vivo. This confirmed AMPs can act in generalist or redundant fashions in some cases. However some AMP-pathogen interactions are remarkably specific. Deletion of just the Drosocin gene explains much of the susceptibility of NF-ÎºB/Imd immune deficient flies to Enterobacter cloacae infection. Meanwhile deletion of just the two Diptericins recapitulates the susceptibility of Imd mutants to P. rettgeri.Contrary to previous assumptions, our findings suggested AMPs are not simple generalist peptides. There are many more short peptide immune genes waiting to be characterized that may be relevant to specific infections. I next investigated three lesser-characterized genes: Baramicin A, DptB, and Drosocin. The Baramicin A gene encodes multiple products, including one peptide (IM22) that was first annotated in my study. I found BaraA is key to the fly defence against pathogenic fungi. Next, I dissected the roles of individual Diptericin genes. Surprisingly, DptB alone is required for survival after infection by a lab isolate of Acetobacter. Finally, I identified Drosocin as the source gene for IM7, a mystery peptide first detected in 1998. A polymorphism in IM7 previously obscured its identification. This polymorphism affects fly defence against Providencia burhodogranariea, where one immune-poor allele effectively rivals deletion of IM7 entirely against this microbe.These AMP-microbe interactions reveal that survival after infection can be mediated at the level of single AMP genes or even com-mon alleles of those genes. Contrary to previous assumptions, it appears the AMP response is composed of silver bullets, wooden stakes, and other specialized defence tools required to fight specific enemies. In this light, the diverse AMPs induced upon infection may be an evolutionary solution to optimize survival: general microbe patterns induce immune signalling, there is a need for timely production of antimicrobial peptides, and so a battery of antimicrobial peptides are produced immediately even though only a few are likely to be relevant for any given pa

EPFL2022

Chargement

The role of immune effectors in controlling Drosophila-microbes interactions

Alice Marra

All live beings are in constant interaction with microorganisms that may be beneficial, deleterious or commensal. Insects in particular live in close contact with microorganisms. This is especially true for species, like the fruit fly Drosophila melanogaster that feed, lay eggs and develop on or close to decomposing organic matter. In contrast to vertebrates, insects did not evolve an adaptive immune system to combat pathogens selectively. They instead rely on surprisingly efficient innate defense mechanisms for the control and clearance of all microbes without any species-specific targeting. Innate immunity encompasses a wide range of mechanisms that rely on direct pathogen recognition and elimination. In addition, metabolic and behavioral responses also strongly affect the outcome of insect interactions with both pathogenic and non-pathogenic bacteria. Although the Drosophila immune system has been extensively described, little is known about the role of immune effectors in tolerating and controlling symbiotic microbes. For this reason, during my PhD studies, I investigated how Drosophila melanogaster immune effectors differentially interact with mutualistic symbionts. First, I investigated the role of some of the host antimicrobials, called antimicrobial peptides and lysozymes, in maintaining the homeostasis of the gut microbiota. I found that both antimicrobial peptides and lysozymes can actively regulate the gut microbiota composition and abundancy, especially during aging. In a second part of my thesis, I got interested in Spiroplasma, a heritable symbiotic bacterium that lives within the fly hemolymph. I characterized the role of the Drosophila iron transporter Transferrin 1 (Tsf1) during Spiroplasma-Drosophila symbiosis. I first showed that mutant flies for tsf1 have an impaired Spiroplasma load, due to iron relocation from the hemolymph to the fat body, where it becomes inaccessible for Spiroplasma. Furthermore, I demonstrated that Spiroplasma scavenges host iron only when it is bound to the protein, which points to Tsf1 and iron transport as a control mechanism for hemolymphatic symbionts. Collectively, my studies contribute to a better understanding of how the innate immune effectors interact with Drosophila microbial symbionts to both regulate and maintain stable, long-lasting, interactions.

EPFL2021

Chargement

Cecropins contribute to Drosophila host defense against a subset of fungal and Gram-negative bacterial infection

Alexia Laurie Carboni, Mark Austin Hanson, Bruno Lemaitre

Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding Cecropins are strongly induced upon infection, pointing to their role in host defense. In Drosophila, four cecropin genes clustered in the genome (CecA1, CecA2, CecB, and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion Delta Cec(A-C) removing the whole cecropin locus. Using the Delta Cec(A-C) deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of Cecropins in the systemic immune response. Delta Cec(A-C) flies were viable and resisted challenge with various microbes as wild-type. However, removing Delta Cec(A-C) in flies already lacking 10 other AMP genes revealed a role for Cecropins in defense against Gram-negative bacteria and fungi. Measurements of pathogen loads confirm that Cecropins contribute to the control of certain Gram-negative bacteria, notably Enterobacter cloacae and Providencia heimbachae. Collectively, our work provides the first genetic demonstration of a role for Cecropins in insect host defense and confirms their in vivo activity primarily against Gram-negative bacteria and fungi. Generation of a fly line (Delta AMP14) that lacks 14 immune inducible AMPs provides a powerful tool to address the function of these immune effectors in host-pathogen interactions and beyond.

OXFORD UNIV PRESS INC2022

Chargement

Afficher plus

The role of immune effectors in controlling Drosophila-microbes interactions

Alice Marra

EPFL2021

EPFL2022