Albumin as a functional carrier solubilizing and facilitating fusidic acid transmembrane delivery into Gram-negative bacteria.

Reversing the bacterial resistance is of great significance and importance. Fusidic acid (FA) is commonly effective against Gram-positive bacterial infections, but most Gram-negative bacteria have intrinsic resistance to FA, primarily due to the strong cell membrane-FA interactions, which highly inhibit the intracellular transport of FA. Herein, we use albumin (bovine serum albumin, BSA) as a bifunctional carrier to solubilize FA and facilitate its transmembrane delivery into Gram-negative bacterial cells. The water solubility of FA is significantly enhanced from 11.87 to 442.20 μg/mL by 5 mg/mL BSA after forming FA-BSA complex. Furthermore, FA-BSA (200 μg/mL) causes 99.96 % viability loss to the model pathogen E. coli upon incubation for 3 h, while free FA or BSA alone shows little activity. Elongation of E. coli cells after treated by FA-BSA is demonstrated by SEM, and the transmembrane transport of FA-BSA is demonstrated by CLSM. Interestingly, increasing the BSA amount substantially reduce the antibacterial activity of FA-BSA, implying an albumin-based transmembrane delivery mechanism may exist. This is the first report regarding successfully reversing the intrinsic resistance of Gram-negative bacteria to FA in the form of FA-BSA. The ready availability of albumin and the simple preparation allows FA-BSA to have great potentials for clinical use.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.