英國研究人員日前報告說,，有些化合物可以通過抑制結(jié)核桿菌中一種酶的功能來殺死這種細菌，這是一種對付結(jié)核桿菌的新方法,，將有助于研發(fā)治療肺結(jié)核的新藥物,。
英國伯明翰大學(xué)等機構(gòu)研究人員在新一期《微生物學(xué)》雜志上報告說，結(jié)核桿菌中一種名為IMPDH的酶對細菌細胞的生存至關(guān)重要,，抑制這種酶的功能就可以殺死結(jié)核桿菌,。研究人員測試了多種相關(guān)化合物，發(fā)現(xiàn)有3種二苯脲類化合物抑制這種酶的效率都在90％以上,。
研究人員說,，這種酶對人類細胞和細菌細胞都很重要，在治療人類癌癥的實踐中，已經(jīng)將它作為藥物靶點來殺滅癌細胞,。而且,，本次研究測試的幾種化合物都是“選擇性活躍”，它們只對結(jié)核桿菌中的這種酶有效,，而不會殺死正常的人體細胞,，因此可以在此基礎(chǔ)上研發(fā)新的治療肺結(jié)核的藥物。
結(jié)核桿菌是引起肺結(jié)核等疾病的病原菌,。肺結(jié)核曾長期被認為是不治之癥,，后來一些抗生素問世后，肺結(jié)核的治療變得較為容易,。但近年來結(jié)核桿菌對已有藥物的耐藥性逐漸增強,，世界衛(wèi)生組織也警告說，肺結(jié)核在全球有卷土重來的趨勢,，因此研究人員一直在致力尋找治療肺結(jié)核的新方法,。（生物谷Bioon.com）
更多閱讀
Science：新藥研制為肺結(jié)核治療鋪平道路
Science：新化合物可阻止結(jié)核桿菌形成細胞壁 有望制成抗肺結(jié)核新藥
Nature Immunology：肺結(jié)核病毒擁有“秘密通道”
PLoS ONE：最早肺結(jié)核可追溯至9千年前
生物谷推薦英文摘要：
Microbiology DOI：10.1099/mic.0.042549-0
Identification of novel diphenyl urea inhibitors of Mt-Guab2 active against Mycobacterium tuberculosis
Veeraraghavan Usha1, Sudagar S Gurcha1, Andrew Lovering1, Adrian J Lloyd2, Athina Papaemmanouil1, Robert C Reynolds3 and Gurdyal S Besra1,4
1 University of Birmingham;
2 University of Warwick;
3 Southern Research Insititute
In contrast to most bacteria which harbor a single inosine monophosphate dehydrogenase (IMPDH) gene, the genomic sequence of Mycobacterium tuberculosis H37Rv predicts three genes encoding IMPDH: guab1, guab2 and guab3. The three genes encoding IMPDH from M. tuberculosis H37Rv were cloned and expressed in Escherichia coli to evaluate functional IMPDH activity. Purified recombinant Mt-Guab2 which uses inosine monophosphate (IMP) as a substrate was identified as the only active Guab ortholog in M. tuberculosis and was optimal at pH 8.5 and 37 °C. Mt-Guab2 was inhibited significantly in vitro by a panel of diphenyl urea-based derivatives, which were also potent anti-mycobacterial agents against M. tuberculosis and Mycobacterium smegmatis with minimum inhibitory concentrations (MICs) in the range of 0.2 to 0.5 μg ml-1. When Mt-Guab2 was over-expressed on a plasmid in trans in M. smegmatis, a diphenyl urea analogue showed a 16-fold increase in MIC. Interestingly, when Mt-Guab orthologs (Mt-Guab1 and 3) were also overexpressed on a plasmid in trans in M. smegmatis they also conferred resistance, suggesting that although these Mt-guab orthologs were inactive in vitro they presumably titrate the effect of the inhibitory properties of the active compounds in vivo.
