Balofloxacin

Balofloxacin is quinolone antibiotic, inhibiting the synthesis of bacterial DNA by interference with the enqyme DNA gyrase.

Alterations of protein complexes and pathways in genetic information flow and response to stimulus contribute to Escherichia coli resistance to balofloxacin.[Pubmed:22729160]

Mol Biosyst. 2012 Sep;8(9):2303-11.

Protein-protein interactions are important biological processes and essential for a global understanding of cell functions. To date, little is known about the protein interactions and roles of the protein interacting networks and protein complexes in bacterial resistance to antibiotics. In the present study, we investigated protein complexes in Escherichia coli exposed to an antibiotic Balofloxacin (BLFX). One homomeric and eight heteromeric protein complexes involved in BLFX resistance were detected. Potential roles of these complexes that are played in BLFX resistance were characterized and categorized into four functional areas: information streams, monosaccharide metabolism, response to stimulus and amino acid metabolic processes. Protein complexes involved in information streams and response to stimulus played more significant roles in the resistance. These results are consistent with previously published mechanisms on the acquired quinolone-resistance through the GyrA-GyrB complex, and two novel antibiotic-resistant pathways were identified: upregulation of genetic information flow and alteration of the response to a stimulus. The balance of the two pathways will be a viable means of reducing BLFX-resistance.

In vitro and in vivo effectiveness evaluation of balofloxacin in experimental Staphylococcus aureus keratitis.[Pubmed:24828089]

J Ocul Pharmacol Ther. 2014 Aug;30(6):482-8.

PURPOSE: To evaluate the effectiveness of Balofloxacin for treatment of experimental Staphylococcus aureus keratitis. METHODS: In vitro testing compared the cellular toxicity of and bacterial susceptibility to Balofloxacin and levofloxacin in human corneal epithelial cells (HCECs). For in vivo testing, experimental bacterial keratitis was induced and treated with Balofloxacin eye drops (0.5%) and levofloxacin eye drops (0.5%). RESULTS: In vitro toxicity examinations showed that Balofloxacin, as well as levofloxacin, had low cytotoxicity in HCECs. Balofloxacin eye drops (0.5%) also showed a similar relative cytotoxicity to levofloxacin eye drops (0.5%). In bacterial susceptibility examinations, both Balofloxacin and levofloxacin significantly reduced S. aureus compared with the untreated control (P<0.001 for both Balofloxacin and levofloxacin). Balofloxacin was more effective than levofloxacin in the treatment of S. aureus bacterial keratitis (P<0.05). In experimental bacterial keratitis treatment testing, Balofloxacin was also more effective than levofloxacin with respect to the parameters of physiological score, histological observation, and bacterial quantitation (P<0.05). CONCLUSIONS: Balofloxacin was safe in the treatment of S. aureus bacterial keratitis, and more effective than levofloxacin. Therefore, Balofloxacin was shown to have potential clinical value in ophthalmic local application.

Myo-inositol improves the host's ability to eliminate balofloxacin-resistant Escherichia coli.[Pubmed:26030712]

Sci Rep. 2015 Jun 1;5:10720.

Antibiotic-resistant mechanisms are associated with fitness costs. However, why antibiotic-resistant bacteria usually show increasing adaptation to hosts is largely unknown, especially from the host's perspective. The present study reveals the host's varied response to Balofloxacin-resistant Escherichia coli (BLFX-R) using an integrated proteome and metabolome approach and identifies myo-inositol and phagocytosis-related proteins as crucial biomarkers. Originally, macrophages have an optimal attractive preference to BLFX-S due to more polarization of BLFX-S than BLFX-R, which renders faster elimination to BLFX-S than BLFX-R. The slower elimination to BLFX-R may be reversed by exogenous myo-inositol. Primarily, myo-inositol depolarizes macrophages, elevating adherence to both BLFX-S and BLFX-R. Since the altered adherence is equal to both strains, the myo-inositol-treated macrophages are free of the barrier to BLFX-R and thereby promote phagocytosis of BLFX-R. This work provides a novel strategy based on metabolic modulation for eliminating antibiotic-resistant bacteria with a high degree of host adaptation.

Downregulation of Na(+)-NQR complex is essential for Vibrio alginolyticus in resistance to balofloxacin.[Pubmed:22465713]

J Proteomics. 2012 May 17;75(9):2638-48.

Increasingly isolated frequency of antibiotic-resistant V. alginolyticus strains in clinic and aquaculture has been reported, but the mechanisms of V. alginolyticus antibiotic resistance are largely absent. In the present study, native/SDS-PAGE based proteomics, which may provide information on protein-protein interaction, was utilized to investigate differential proteins of V. alginolyticus in resistance to Balofloxacin. Ten proteins were altered, in which V12G01_04671, V12G01_00457, V12G01_15927, V12G01_15240, NqrA (spot 26), and NqrF (spot 30) were downregulated, while V12G01_22043, TolC, V12G01_15130, V12G01_19297 were upregulated. Importantly, the two components of Na(+)-NQR complex, NqrA and NqrF, were vertically lined and was further investigated. Western blotting assay indicated that downregulation of the two proteins contrasted sharply with upregulation of a control protein TolC, which was consistent with the result obtained from 2-DE gel analysis. Furthermore, overexpression of NqrA, NqrF and TolC resulted in decrease and elevation of bacterial survival ability in medium with Balofloxacin, respectively. These results indicate that downregulation of Na(+)-NQR complex is essential for V. alginolyticus resistance to Balofloxacin. This is the first report on the role of Na(+)-NQR complex in antibiotic resistance. This finding highlights the way to an understanding of antibiotic-resistant mechanisms in content of metabolic regulation.