Engineering Lactobacillus rhamnosus GG and GR-1 to express HIV-inhibiting griffithsin
| Autor: | Irina Spacova, Jan Balzarini, Jos Vanderleyden, Dominique Schols, Marianne F.L. van den Broek, Tine Verhoeven, Sarah Lebeer, Mariya I. Petrova |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Signal peptide Anti-HIV Agents 030106 microbiology Gene Expression Protein Sorting Signals Virus Replication Cell Line Microbiology law.invention 03 medical and health sciences Probiotic Bacterial Proteins Lactobacillus rhamnosus law Lectins Lactobacillus Actinohivin Extracellular Humans Pharmacology (medical) Promoter Regions Genetic Biology Griffithsin Carbohydrate-binding agents biology Lacticaseibacillus rhamnosus Probiotics Pharmacology. Therapy HIV food and beverages General Medicine biology.organism_classification Recombinant Proteins 030104 developmental biology Infectious Diseases Metabolic Engineering HIV-1 biology.protein Recombinant DNA Human medicine Plant Lectins Engineering sciences. Technology Intracellular |
| Zdroj: | International journal of antimicrobial agents |
| ISSN: | 0924-8579 |
| DOI: | 10.1016/j.ijantimicag.2018.07.013 |
| Popis: | Probiotic bacteria are being explored for the in situ delivery of various therapeutic agents. In this study, we aimed to express two HIV-inhibiting lectins, actinohivin (AH) and griffithsin (GRFT), in the probiotic strains Lactobacillus rhamnosus GG and L. rhamnosus GR-1 for gastrointestinal and vaginal mucosal delivery, respectively. Constructs were generated for the intracellular and extracellular production of AH and GRFT under the control of the promoter of their Major Secreted Protein Msp1. Also, intracellular expression of GRFT was investigated under the control of the nisA promoter from the inducible nisin-controlled expression (NICE) system. For the extracellular localization, the signal leader peptide of Msp1/p75 from L. rhamnosus GG was translationally fused with the genes encoding AH and GRFT. Construction of recombinant strains expressing the AH monomer and dimer was unsuccessful, probably due to the intracellular toxicity of AH for the lactobacilli. On the other hand, recombinant strains for intra- and extracellular production of GRFT by L. rhamnosus GG and GR-1 were successfully constructed. The highest expression levels of recombinant GRFT were observed for the constructs under the control of the inducible nisA promoter and we demonstrated anti-HIV activity against an M-tropic and a T-tropic HIV-1 strain. We can conclude that recombinant Lactobacillus expressing anti-HIV lectins could contribute to the development of enhanced probiotic strains that are able to inhibit HIV transmission and subsequent replication, although further research and development are required. ispartof: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS vol:52 issue:5 pages:599-607 ispartof: location:Netherlands status: published |
| Databáze: | OpenAIRE |
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