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Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection
Valappil, Sabeel P. Abou Neel, Ensanya A. Zakir Hossain, Kazi M. Paul, Willi Cherukaraveedu, Durgadas Wade, Benjamin Ansari, Tahera I Hope, Christopher K. Higham, Susan M. Sharma, Chandra P.
Valappil, Sabeel P.
Abou Neel, Ensanya A.
Zakir Hossain, Kazi M.
Paul, Willi
Cherukaraveedu, Durgadas
Wade, Benjamin
Ansari, Tahera I
Hope, Christopher K.
Higham, Susan M.
Sharma, Chandra P.
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EPub Date
Publication Date
2023-12-19
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Abstract
Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections.
Citation
Valappil, S. P., Abou Neel, E. A., Hossain, K. M. Z., Paul, W., Cherukaraveedu, D., Wade, B., Ansari, T. I., Hope, C. K., Higham, S. M., & Sharma, C. P. (2024). Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection. International Journal of Biological Macromolecules, 258(1), article-number 128838. https://doi.org/10.1016/j.ijbiomac.2023.128838
Publisher
Elsevier
Journal
International Journal of Biological Macromolecules
Research Unit
DOI
10.1016/j.ijbiomac.2023.128838
PubMed ID
PubMed Central ID
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Article
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Series/Report no.
ISSN
0141-8130