| Objective: Plague, one of the most devastating diseases of human history,is caused by Yersinia pestis.Endemic ares for this disease widely exist in Asia,Afica and America,where the occasional epizootics of animal plague pose great threats to public health. Plague has been classified as a reemerging disease by the Word Health Organization due to the wordwide increasing incidence of human plague. Case of bubonic plague can be well controlled by timely antibiotic treatment. However, the pneumonic or septicemic plague is difficult to be treated with antibiotic therap.The recent isolation of a multiple antibiotic resistant strain of Y.pestis indicates that the longer term potential for the use of antibiotics to treat plague is less certain.It is important to find novel targets for drug development for this deadly pathogen.As a complementary medical system to western medicine,traditional Chinese medicine (TCM) provides a unique theoretical and practical approach to treatment of diseases over thousands of years, in particular on their antibacterial properties.Coptidis rhizoma(Huanglian in chinese)has been used for more than two thousand years by TCM physician for treatment of intestinal infection including acute gastroenteritis, cholera and bacillary dysentery which can be linked to their antibacreial, antiviral and anti-inflammatory effects. So,we presumed that coptidis rhizome is also an ideal medicine to against Y.pestis.It is imporotant to extensively understand the molecular mechanism of action of the TCM and attempts should be conducted as well for the development of new antibiotics.The availability of the genome sequence and the development of DNA microarray to profile the transcriptome have opened a window for monitor global changes in gene expression inY.pestis.Here we also used the global-genome DNA microarray to investigate the global transcriptional response of Y.pestis triggered by the treatment of Coptidis Rhizome, giving an overall picture of the molecular mechanism of the action of the TCM in vanquishing this deadly pathogen.Methods: In this study, The minimal inhibition concentrations (MIC) of the Coptidis Rhizome to Y.pestis were determined by liquid dilution method. The gene expression profile of Y.pestis were performed after exposure to Coptis rhizome at concentration of 10×MIC for 30 min. DNA microarray was used to investigate the transcriptional response of Y.pestis to Coptis rhizome.Total RNA were extracted and purified from Y.pestis and reverse-transcribed to cDNA, labeled by Cy-dye,the labeled probes were hybridized to the microarray,Then the results were compared and validated with quantitative Real time-PCR.Results:1. 4005 genes were successfully amplified,and developed a batched of good quality whole-genome DNA microarray. 2. Under the effect of Coptidis Rhizome,360 genes were differentially expressed ,among them 333 and 27 genes altered respectively. 3. Microarray data and qRT-PCR results showed a positive correlation.(r=0.92).Conclusion:Our results shows that the general gene expression changes of Y. pestis in response to Coptis rhizome,The upregulation of genes related to cell envelope was a significent change in response to Coptis rhizome. Genes encoding the metabolism and transport/binding proteins were also the major changed genes of the Y. pestis. The study revealed global transcriptional changes of Y. pestis in response to Coptis rhizome, providing insights into the mechanisms of action of Coptis rhizome against Y. pestis.
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