The anti-tuberculosis activity of metal complexes of fusaric acid and their effect on gene expressions of M.tuberculosis

Abstract

Abstract: Objective To observe in vitro antituberculosis activity of copper ion complex and cadmium ion complex of fusaric acid, and their effects on the gene expressions of M.tuberculosis (Mtb) H37Rv. Methods The anti-tuberculosis activities of copper ion complex and cadmium ion complex of fusaric acid were determined for three times by Kind-Bauer method, and their minimum inhibitory concentrations (MICs) were detected twice by the absolute concentration method.The differences of the gene expressions of Mtb H37Rv between the compound group and non-compound control group were measured twice with DNA chips. Results The antibacterial diameters of cadmium complex and cupric complex of fusaric acid on the BCG plates were (30.0±0.8) mm and (30.4±0.6) mm, respectively. The MIC of cupric complex of fusaric acid on Mtb H37Rv was 10 μg/ml. The MIC of cadmium complex of fusaric acid on multi-drug-resistant Mtb was 7.5 μg/ml, which was lower than that of streptomycin (S, MIC=25 μg/ml) and rifampicin (RFP,MIC=25 μg/ml). The MIC of cupric complex of fusaric acid on Mtb clinical isolate（No.0907961，resistant to S and EMB) was 10 μg/ml, which was lower than that of S (MIC=20 μg/ml); and the MIC of cadmium complex of fusaric acid was 5 μg/ml, which was lower than that of S (MIC=20 μg/ml) and EMB (MIC=6.4 μg/ml). Of 3875 genes tested by the DNA array, 23 genes (10 known functional genes) were significantly different in copper ion complex group, and 28 genes (11 known functional genes) in cadmium ion complex group compared with the control groups. The functions of these differential genes were involved in nucleotide, lipid, energy, coenzyme, amino acid metabolism, DNA replication, transcription, translation, post-translational modification, biosynthesis of cell membranes etc. Conclusion Metal complexes of fusaric acid appeared considerable in vitro anti-tuberculosis activity, especially inhibitory activities of the compounds on some drug-resistant Mtb strains appeared higher than that of the first-line agents.Therefore, they could be used as anti-tuberculosis lead compounds. The genes with differential expressions showed by the DNA chip provide a valuable foundation for further study on their antibacterial mechanism.

Key words: Fusaric acid, Coordination complexes, Antitubercular agents, Oligonucleotide array sequence analysis, Gene expression

WANG Juan, HUANG Yu-hong, CHEN Yi, LI Yan, PENG Yi, PAN Jia-hui, WANG Jun, LIN Yong-cheng, LAI Xiao-min. The anti-tuberculosis activity of metal complexes of fusaric acid and their effect on gene expressions of M.tuberculosis[J]. Chinese Journal of Antituberculosis, 2012, 34(04): 224-228.

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