Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection

• Published in: International journal of biological macromolecules Vol. 258; no. Pt 1; p. 128838
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2024
• Subjects: Antibacterial; Gallium; In vivo wound healing; Lactoferrin; Pseudomonas aeruginosa; Pseudomonas aeruginosa; Gallium; Lactoferrin; In vivo wound healing; Antibacterial
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.128838

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.