The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications.
Lantibiotics are peptides, produced by bacteria, that contain the noncanonical amino acid lanthionine and many of them exhibit antibacterial activities. The labyrinthopeptin A1 (LabyA1) is a prototype peptide of a novel class of carbacyclic lantibiotics. Here, we extensively evaluated its broad-spec...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/872bea6f6dfd45b8b8ca202f5c18c5d9 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:872bea6f6dfd45b8b8ca202f5c18c5d9 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:872bea6f6dfd45b8b8ca202f5c18c5d92021-11-18T07:44:09ZThe lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications.1932-620310.1371/journal.pone.0064010https://doaj.org/article/872bea6f6dfd45b8b8ca202f5c18c5d92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23724015/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Lantibiotics are peptides, produced by bacteria, that contain the noncanonical amino acid lanthionine and many of them exhibit antibacterial activities. The labyrinthopeptin A1 (LabyA1) is a prototype peptide of a novel class of carbacyclic lantibiotics. Here, we extensively evaluated its broad-spectrum activity against HIV and HSV in vitro, studied its mechanism of action and evaluated potential microbicidal applications. LabyA1 exhibited a consistent and broad anti-HIV activity (EC50s: 0.70-3.3 µM) and anti-HSV activity (EC50s: 0.29-2.8 µM) in cell cultures. LabyA1 also inhibited viral cell-cell transmission between persistently HIV-infected T cells and uninfected CD4(+) T cells (EC50∶2.5 µM) and inhibited the transmission of HIV captured by DC-SIGN(+)-cells to uninfected CD4(+) T cells (EC50∶4.1 µM). Time-of-drug addition studies revealed that LabyA1 acts as an entry inhibitor against HIV and HSV. Cellular and virus binding studies combined with SPR/FLIPR technology showed that LabyA1 interacted with the HIV envelope protein gp120, but not with the HIV cellular receptors. LabyA1 also demonstrated additive to synergistic effects in its anti-HIV-1 and anti-HSV-2 activity with anti(retro)viral drugs in dual combinations such as tenofovir, acyclovir, saquinavir, raltegravir and enfuvirtide. LabyA1 can be considered as a novel lead peptide as it had profound antiviral activity against HIV and HSV. Pre-treatment of PBMCs with LabyA1 neither increased the expression of the activation markers CD69 and CD25, nor enhanced HIV replication, nor significantly induced various inflammatory cytokines/chemokines. LabyA1 also did not affect the growth of vaginal Lactobacilli populations. Based on the lack of toxicity on the vaginal Lactobacillus strains and its synergistic/additive profile in combination with clinically approved anti(retro)virals, it deserves further attention as a potential microbicide candidate in the prevention of sexual transmitted diseases.Geoffrey FérirMariya I PetrovaGraciela AndreiDana HuskensBart HoorelbekeRobert SnoeckJos VanderleydenJan BalzariniStefan BartoschekMark BrönstrupRoderich D SüssmuthDominique ScholsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64010 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Geoffrey Férir Mariya I Petrova Graciela Andrei Dana Huskens Bart Hoorelbeke Robert Snoeck Jos Vanderleyden Jan Balzarini Stefan Bartoschek Mark Brönstrup Roderich D Süssmuth Dominique Schols The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| description |
Lantibiotics are peptides, produced by bacteria, that contain the noncanonical amino acid lanthionine and many of them exhibit antibacterial activities. The labyrinthopeptin A1 (LabyA1) is a prototype peptide of a novel class of carbacyclic lantibiotics. Here, we extensively evaluated its broad-spectrum activity against HIV and HSV in vitro, studied its mechanism of action and evaluated potential microbicidal applications. LabyA1 exhibited a consistent and broad anti-HIV activity (EC50s: 0.70-3.3 µM) and anti-HSV activity (EC50s: 0.29-2.8 µM) in cell cultures. LabyA1 also inhibited viral cell-cell transmission between persistently HIV-infected T cells and uninfected CD4(+) T cells (EC50∶2.5 µM) and inhibited the transmission of HIV captured by DC-SIGN(+)-cells to uninfected CD4(+) T cells (EC50∶4.1 µM). Time-of-drug addition studies revealed that LabyA1 acts as an entry inhibitor against HIV and HSV. Cellular and virus binding studies combined with SPR/FLIPR technology showed that LabyA1 interacted with the HIV envelope protein gp120, but not with the HIV cellular receptors. LabyA1 also demonstrated additive to synergistic effects in its anti-HIV-1 and anti-HSV-2 activity with anti(retro)viral drugs in dual combinations such as tenofovir, acyclovir, saquinavir, raltegravir and enfuvirtide. LabyA1 can be considered as a novel lead peptide as it had profound antiviral activity against HIV and HSV. Pre-treatment of PBMCs with LabyA1 neither increased the expression of the activation markers CD69 and CD25, nor enhanced HIV replication, nor significantly induced various inflammatory cytokines/chemokines. LabyA1 also did not affect the growth of vaginal Lactobacilli populations. Based on the lack of toxicity on the vaginal Lactobacillus strains and its synergistic/additive profile in combination with clinically approved anti(retro)virals, it deserves further attention as a potential microbicide candidate in the prevention of sexual transmitted diseases. |
| format |
article |
| author |
Geoffrey Férir Mariya I Petrova Graciela Andrei Dana Huskens Bart Hoorelbeke Robert Snoeck Jos Vanderleyden Jan Balzarini Stefan Bartoschek Mark Brönstrup Roderich D Süssmuth Dominique Schols |
| author_facet |
Geoffrey Férir Mariya I Petrova Graciela Andrei Dana Huskens Bart Hoorelbeke Robert Snoeck Jos Vanderleyden Jan Balzarini Stefan Bartoschek Mark Brönstrup Roderich D Süssmuth Dominique Schols |
| author_sort |
Geoffrey Férir |
| title |
The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| title_short |
The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| title_full |
The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| title_fullStr |
The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| title_full_unstemmed |
The lantibiotic peptide labyrinthopeptin A1 demonstrates broad anti-HIV and anti-HSV activity with potential for microbicidal applications. |
| title_sort |
lantibiotic peptide labyrinthopeptin a1 demonstrates broad anti-hiv and anti-hsv activity with potential for microbicidal applications. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/872bea6f6dfd45b8b8ca202f5c18c5d9 |
| work_keys_str_mv |
AT geoffreyferir thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT mariyaipetrova thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT gracielaandrei thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT danahuskens thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT barthoorelbeke thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT robertsnoeck thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT josvanderleyden thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT janbalzarini thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT stefanbartoschek thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT markbronstrup thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT roderichdsussmuth thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT dominiqueschols thelantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT geoffreyferir lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT mariyaipetrova lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT gracielaandrei lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT danahuskens lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT barthoorelbeke lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT robertsnoeck lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT josvanderleyden lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT janbalzarini lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT stefanbartoschek lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT markbronstrup lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT roderichdsussmuth lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications AT dominiqueschols lantibioticpeptidelabyrinthopeptina1demonstratesbroadantihivandantihsvactivitywithpotentialformicrobicidalapplications |
| _version_ |
1718423047187202048 |