Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess
Serum-induced iron-acquisition systems and TonB contribute to virulence in Klebsiella pneumoniae causing primary pyogenic liver abscess
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DOI：
10.1086/588383
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发表时间：
2008-06-15
影响因子：
6.4
通讯作者：
Wang, Jin-Town
中科院分区：
文献类型：
--
作者：
Hsieh, Pei-Fang;Lin, Tzu-Lung;Wang, Jin-Town
背景肺炎克雷伯菌已成为原发性化脓性肝脓肿的主要致病菌。K.用人血清刺激pneumoniae，用基因芯片分析基因表达。三个假定的铁获取系统，耶尔森氏菌高致病性岛（HPI），iucABCDiutA和iroA（iroNDCB），在PLA相关的K。鉴定肺炎菌株。通过铁载体摄取试验，证实这3个系统是铁载体依赖的铁获取系统。只有irp 2-iuc-iroA三重突变体在小鼠中显示出降低的毒力。对K. pneumoniae菌株NTUH-K2044鉴定了10个推定的铁摄取系统。这10个系统中有7个是TonB依赖性的，包括耶尔森氏菌HPI、iucABCDiutA和iroA。tonB缺失突变体被证明具有显著的毒力衰减。用tonB突变体免疫导致胞外多糖抗体的血清转化和对随后暴露于亲本菌株的保护效力。铁吸收系统是K. pneumoniae中表达，对血清的应答高度上调。虽然NTUH-K2044中存在多个铁转运系统，但所有3个位点（irp 2、iuc和iroA）的突变对于降低毒力是必要的。tonB突变体是一种潜在的疫苗候选者，因为它可以诱导针对野生型菌株攻击的显著保护性免疫应答。
Background. Klebsiella pneumoniae has become the predominant pathogen causing primary pyogenic liver abscess (PLA).Methods. K. pneumoniae was stimulated by human serum, and gene expression was analyzed by microarray.Results. Three putative iron acquisition systems, Yersinia high-pathogenicity island (HPI), iucABCDiutA, and iroA(iroNDCB), that increased in expression and predominated in PLA-associated K. pneumoniae strains were identified. By use of siderophore uptake assays, these 3 systems were confirmed to be siderophore-dependent iron acquisition systems. Only the irp2-iuc-iroA triple mutant showed decreased virulence in mice. Full-genome analysis of K. pneumoniae strain NTUH-K2044 identified 10 putative iron uptake systems. Seven of these 10 systems were TonB dependent, including Yersinia HPI, iucABCDiutA, and iroA. A tonB deletion mutant was demonstrated to have profound attenuation of virulence. Immunization with the tonB mutant resulted in seroconversion of extracellular polysaccharide antibodies and protective efficacy against subsequent exposure to the parental strain.Conclusions. Iron uptake systems were the genes in K. pneumoniae that were highly up-regulated in response to sera. Although there are multiple iron transporter systems in NTUH-K2044, a mutation in all 3 loci (irp2, iuc, and iroA) is necessary to decrease virulence. The tonB mutant is a potential vaccine candidate because it can induce a significant protective immune response against challenge with a wild-type strain.