Development of nanobody-conjugated LL37 for synergistic therapy against MDR Acinetobacter baumannii
1
Issued Date
2026-03-31
Resource Type
eISSN
23795042
Scopus ID
2-s2.0-105034777773
Pubmed ID
41649287
Journal Title
Msphere
Volume
11
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Msphere Vol.11 No.3 (2026) , e0077925
Suggested Citation
Thaiprayoon A., Oonanant W., Boonsilp S., Submunkongtawee N., Longsompurana P., Moonmangmee D., Riangrungroj P., Leelawattanachai J., Tabtimmai L., Kruse A.C., DeLisa M.P., Havanapan P.O., Waraho-Zhmayev D. Development of nanobody-conjugated LL37 for synergistic therapy against MDR Acinetobacter baumannii. Msphere Vol.11 No.3 (2026) , e0077925. doi:10.1128/msphere.00779-25 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116134
Title
Development of nanobody-conjugated LL37 for synergistic therapy against MDR Acinetobacter baumannii
Author's Affiliation
Harvard Medical School
Cornell University College of Engineering
King Mongkut's University of Technology Thonburi
King Mongkut's University of Technology North Bangkok
Thailand National Center for Genetic Engineering and Biotechnology
Thailand National Nanotechnology Center
Institute of Molecular Biosciences, Mahidol University
Vajira Hospital
Cornell Institute of Biotechnology
Cornell University College of Engineering
King Mongkut's University of Technology Thonburi
King Mongkut's University of Technology North Bangkok
Thailand National Center for Genetic Engineering and Biotechnology
Thailand National Nanotechnology Center
Institute of Molecular Biosciences, Mahidol University
Vajira Hospital
Cornell Institute of Biotechnology
Corresponding Author(s)
Other Contributor(s)
Abstract
Multidrug resistance (MDR) of the pathogen Acinetobacter baumannii is a major challenge to global healthcare due to the limited treatment options. The emergence of MDR bacteria necessitates innovative therapeutic approaches, especially given the associated economic burden and the rapid spread of infections. Conventional treatments such as antibiotics and vaccines face significant obstacles. Antimicrobial peptides (AMPs) such as LL37 have potential as an alternative treatment due to their broad-spectrum activity and ability to target specific bacterial structures such as the outer membrane protein A (OmpA). The efficacy of AMPs can be enhanced by using nanobodies (Nbs) that bind to bacterial OmpA, guiding LL37 precisely to its target. In this study, A. baumannii OmpA (AbOmpA)-specific Nbs (NbO7 and NbO13) were efficiently isolated through magnetic-activated cell sorting-based screening of a yeast surface display library, eliminating the need for specialized equipment. Nbs exhibited specific, dose-dependent binding to the target. Conjugation of Nbs with LL37 effectively inhibited the growth of MDR A. baumannii. This approach leverages the natural antimicrobial properties of AMPs and enhances their specificity and effectiveness by targeting bacterial cell surface proteins. LL37-conjugated AbOmpA-Nbs present a promising therapeutic strategy against MDR A. baumannii and other resistant pathogens.IMPORTANCEMultidrug-resistant (MDR) Acinetobacter baumannii poses a major global health threat due to its resistance to nearly all available antibiotics and its persistence in hospital settings. This challenge underscores the urgent need for new therapeutic approaches beyond conventional drugs. In this study, we developed an innovative strategy that combines the human antimicrobial peptide LL37 with nanobodies (Nbs) targeting the outer membrane protein A (OmpA), a key virulence and survival factor of A. baumannii. OmpA-specific Nbs were efficiently isolated from a fully synthetic library using a simple, low-cost selection approach without animal immunization. When conjugated with LL37, these Nbs bound specifically to OmpA and strongly inhibited MDR A. baumannii growth in vitro. Our findings introduce a simple yet powerful platform for generating targeted Nb-peptide conjugates, offering strong potential for adaptation against other antibiotic-resistant pathogens and contributing to the development of next-generation biologics to overcome antibiotic limitations.