Publication
Title
Engineering Lactobacillus rhamnosus GG and GR-1 to express HIV-inhibiting griffithsin
Author
Abstract
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.
Language
English
Source (journal)
International journal of antimicrobial agents. - Amsterdam
Publication
Amsterdam : 2018
ISSN
0924-8579
Volume/pages
52 :5 (2018) , p. 599-607
ISI
000449571300008
Pubmed ID
30040991
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Molecular analysis of protein glycosylation in beneficial bacteria.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 05.12.2018
Last edited 11.09.2021
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