oxyR, a LysR-Type Regulator Involved in Klebsiella pneumoniae Mucosal and Abiotic Colonization
oxyR, a LysR-Type Regulator Involved in Klebsiella pneumoniae Mucosal and Abiotic Colonization
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DOI：
10.1128/iai.00837-09
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Forestier, Christiane
中科院分区：
文献类型：
--
作者：
Hennequin, Claire;Forestier, Christiane
在肺炎克雷伯菌医院感染中，胃肠道定植是第一个事件，其次是膀胱或呼吸道定植或进入血液。为了在宿主体内生存，细菌必须具有特定的特征并克服多重压力。OxyR是一种保守的细菌转录因子，通过促进生物膜的形成、菌毛表达和粘膜定植，在上调抗氧化应激防御机制和致病机制中发挥关键作用。在测序的肺炎克雷伯菌基因组中检测到OXR的同源物，并从LM21野生型菌株中扩增出该同源物。为了确定加氧酶R在肺炎克雷伯菌宿主相互作用过程中的作用，构建了加氧酶R等基因突变体，并对其行为进行了评估。当浓度低于10(7)ml(-1)时，氧R缺陷型生物很容易被微摩尔浓度的H(2O)O(2)杀死，并表现出典型的需氧表型。该突变株在生物膜形成和1、3型菌毛基因表达方面存在缺陷。此外，Ox R突变体不能在小鼠胃肠道定植，体外实验表明它与Int-407和HT-29肠上皮细胞的粘附性存在缺陷。在恶劣条件下，Ox R突变体的行为也被确定，复制在胃肠道环境中遇到的压力：Ox R缺失导致对胆汁和酸应激更敏感，但对渗透应激不敏感。这些结果表明Ox R在肺炎克雷伯菌胃肠道定植中的多效性作用。
Colonization of the gastrointestinal tract is the first event in Klebsiella pneumoniae nosocomial infections, followed by colonization of the bladder or respiratory tract or entry into the bloodstream. To survive in the host, bacteria must harbor specific traits and overcome multiple stresses. OxyR is a conserved bacterial transcription factor with a key role both in the upregulation of defense mechanisms against oxidative stress and in pathogenesis by enhancing biofilm formation, fimbrial expression, and mucosal colonization. A homolog of oxyR was detected in silico in the K. pneumoniae sequenced genome and amplified from the LM21 wild-type strain. To determine the role of oxyR in K. pneumoniae host-interaction processes, an oxyR isogenic mutant was constructed, and its behavior was assessed. At concentrations lower than 10(7) ml(-1), oxyR-deficient organisms were easily killed by micromolar concentrations of H(2)O(2) and exhibited typical aerobic phenotypes. The oxyR mutant was impaired in biofilm formation and types 1 and 3 fimbrial gene expression. In addition, the oxyR mutant was unable to colonize the murine gastrointestinal tract, and in vitro assays showed that it was defective in adhesion to Int-407 and HT-29 intestinal epithelial cells. The behavior of the oxyR mutant was also determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment: deletion of oxyR resulted in higher sensitivity to bile and acid stresses but not to osmotic stress. These results show the pleiotropic role of oxyR in K. pneumoniae gastrointestinal colonization.