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Blocking pathogenic Leptospira invasion with aptamer molecules targeting outer membrane LipL32 protein.
- Source :
-
Microbes and infection [Microbes Infect] 2024 May-Jun; Vol. 26 (4), pp. 105299. Date of Electronic Publication: 2024 Jan 14. - Publication Year :
- 2024
-
Abstract
- This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words).<br />Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.<br /> (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Mice
Disease Models, Animal
Kidney microbiology
Kidney pathology
Aptamers, Nucleotide pharmacology
Bacterial Outer Membrane Proteins metabolism
Bacterial Outer Membrane Proteins genetics
Leptospira drug effects
Leptospira pathogenicity
Leptospira metabolism
Leptospirosis microbiology
Leptospirosis drug therapy
Lipoproteins antagonists & inhibitors
Lipoproteins metabolism
SELEX Aptamer Technique
Subjects
Details
- Language :
- English
- ISSN :
- 1769-714X
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Microbes and infection
- Publication Type :
- Academic Journal
- Accession number :
- 38224944
- Full Text :
- https://doi.org/10.1016/j.micinf.2024.105299