2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38228Klebsiella pneumoniae is an important opportunistic pathogen which can cause suppurative infection, pneumonia, urinary tract infection and septicemia in immunocompromised individuals. Although K. pneumoniae can be isolated with high frequency, little is known regarding the molecular basis of its pathogenesis and unusual prevalence in Taiwan. It would be particularly intriguing to understand the mechanisms that an opportunistic pathogen, such as K. pneumoniae uses to adapt itself from environment and achieves a successful infection in the human host. These mechanisms enable K. pneumoniae to switch from a physiological program that permits rapid growth in the presence of abundant nutrients to one that enhances survival under a variety of stressful situations within the hosts. Here we propose to study the regulation of the stress-responsive genes of K. pneumoniae and their functions in the overall physiology and the virulence of K. pneumoniae. Several genome-wide approaches will be performed. Briefly, transcriptome analysis of candidate stress-responsive genes in K. pneumoniae will be conducted upon a variety of stressful conditions. Gene-specific knockout mutants of regulatory genes identified to be responsible for several key stress responsiveness will be generated; their physiological characteristics and pathogenic capacities will be simultaneously determined in several infectious models established. To get insights of the regulatory interplay of stress-responsive genes involved in the pathogenesis of K. pneumoniae, transcriptome analysis of stress regulons with be performed reciprocally in the mutant backgrounds of other stress regulons through measuring the bioluminescence of transcriptional luxCDABE reporters introduced into respective control regions. By completion of the project, improved understanding of the molecular basis from stress responsiveness to virulence is expected to the development of new vaccines or novel antimicrobials for a better control of the Klebsiella infections.克雷白氏肺炎桿菌（Klebsiella pneumoniae）是臨床上極為重要的伺機性感染病原 菌，經常在免疫缺損的病人造成化膿性感染，肺炎，尿路感染及敗血症。 雖然克 雷白氏菌的感染率節節升高，對於該菌致病的分子機轉及其感染在台灣的高普遍性 卻仍不清楚。 我們特別感興趣的是像克雷白氏這類伺機性感染的病原細菌究竟是 透過何種機轉在環境轉換中自我調適以在宿主體內成功造成感染；藉由這類機轉的 表現，細菌可由養分充足環境中快速生長的生理狀態轉換為因應宿主體內逆境的最 適生存模式。 在本計畫中我們將運用基因體學方法研究克雷白氏菌壓力反應基因 的調控機轉以及這些逆境基因在該菌生理及致病上的功能。 計畫執行初期我們將 針對所有克雷白氏菌的壓力反應基因在不同逆境下的表現量進行轉錄體分析，根據 這些壓力基因的表現圖譜，所有在調控網路中扮演樞紐角色的基因將建構其專一基 因缺損的突變菌株。 這些逆境基因的突變菌株的基本生理特性與其致病能力將在 數個已建立的細菌與動物感染模式中與野生型的克雷白氏菌株進行分析比較。 我 們將藉由測定不同壓力反應基因上游調控區中載入之轉錄報告基因組的生物冷光在 其他逆境突變菌株內的表現量以深入了解這些逆境基因的表現調控網路。 本計畫 的完成將使我們深入了解在克雷白氏菌的致病過程中，細菌逆境反應所扮演的生理 角色以及其與其它致病決定因子間的交互作用。 此外，這些結果也將幫助我們找 到有用的藥物標的分子以提供未來抗菌藥物的篩選。克雷白氏肺炎桿菌轉錄體分析逆境反應基因致病機轉Klebsiella pneumoniaetranscriptome analysisstress regulonspathogenesisProject