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Blocking pathogenic Leptospira invasion with aptamer molecules targeting outer membrane LipL32 protein
Shen-Hsing Hsu1, Huang-Yu Yang2, Chia-Chen Chang1
1Kidney Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
Microbes and Infection
|January 15, 2024
Summary
Researchers developed aptamers (L32APs) targeting Leptospira LipL32 to block bacterial invasion. L32AP treatment improved survival and reduced kidney damage in animal models, showing therapeutic potential.
Area of Science:
- Molecular Biology
- Biotechnology
- Infectious Diseases
Background:
- Leptospira are pathogenic bacteria causing leptospirosis.
- LipL32 is a key lipoprotein involved in Leptospira invasion.
- Developing targeted therapies against Leptospira is crucial.
Purpose of the Study:
- To develop high-affinity aptamers targeting LipL32.
- To evaluate the specificity and inhibitory potential of these aptamers.
- To assess the therapeutic efficacy of aptamers against Leptospira infection in vivo.
Main Methods:
- Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate LipL32 aptamers (L32APs).
- Binding affinity, specificity, and inhibition of LipL32-extracellular matrix (ECM) interaction were assessed.
- In vivo studies in animal models evaluated L32AP treatment effects on survival, bacterial load, and kidney damage.
Main Results:
- Three high-affinity L32APs were identified, showing selective binding to pathogenic Leptospira.
- L32APs effectively inhibited LipL32-ECM interaction and Leptospira invasion.
- In animal models, L32AP treatment significantly improved survival rates, reduced bacterial colonization, and mitigated kidney injury.
Conclusions:
- Functional aptamers (L32APs) targeting pathogenic Leptospira were successfully developed.
- L32APs demonstrate high affinity, pathogen selectivity, and inhibit bacterial invasion and ECM interaction.
- Aptamer therapy shows promise for treating Leptospira infections and reducing associated kidney damage.
