Fusidic acid in a tertiary hospital: an observational study focusing on prescriptions, tolerance and susceptibility of Staphylococcus and Cutibacterium spp. strains from bone samples

Romaru, Juliette; Limelette, Anne; Lebrun, Delphine; Bonnet, M.; Garnier, V. Vernet; Nguyen, Yohan

doi:10.1007/s10096-022-04469-6

Cited by 1 publication

(3 citation statements)

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“…Interestingly, there are a lot of obviously elongated E. coli cells after treatment with the FA-PC (hollow arrows indicate the significantly elongated bacteria cells, Figure 4A). Such an elongation implies that the cell division of E. coli is inhibited by the FA-PC, which may be relevant to the antibacterial mechanism of FA (binding to elongation factor G [13,14]). In the case of P. aeruginosa, the free FA also had little effect on the cell morphology, but the significant elongation of P. aeruginosa cells was found after treatment with the FA-PC (hollow arrows indicate the significantly elongated bacteria cells, Figure 4B), the same as that found in E. coli cells.…”

Section: Morphology Changes In Bacteria Cellsmentioning

confidence: 99%

“…As shown in Figure 5C, the bacteria cells treated with the C6-PC have a green fluorescence intensity of 30.6, significantly higher than the green fluorescence intensity of 6.0 seen These SEM images demonstrate the FA-PC-caused elongation of Gram-negative bacteria cells for the first time and support the antibacterial quantitative data in Figures 2 and 3. As we know, the action target of FA is the elongation factor G located on the ribosome in the cytoplasm [11][12][13][14]. In this regard, we have reason to believe that the FA-PC is successfully delivered into Gram-negative bacteria cells via transmembrane transportation, and this needs further investigation.…”

Section: Intracellular Delivery Of Drug-phospholipid Complexmentioning

confidence: 99%

“…Fusidic acid (FA), a steroidal antibiotic, is commonly used for the treatment of staphylococcal infections, including skin, bone and joint infections [8][9][10]. The antibacterial mechanism of FA is based on its irreversible binding to the elongation factor G (EF-G) located on the ribosome [11][12][13][14]. Consequently, the translocation of the nascent polypeptide chain from the A site to the P site, the formulation of the peptide bond and the release of the ribosome complex on reaching the stop codon are all blocked [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Reversing the Natural Drug Resistance of Gram-Negative Bacteria to Fusidic Acid via Forming Drug–Phospholipid Complex

Liu,

Lai,

et al. 2024

Bioengineering

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Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA–phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA–phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss of E. coli and 99.1% loss of P. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use.

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Section: Morphology Changes In Bacteria Cellsmentioning

confidence: 99%