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Iron content differs between Francisella tularensis subspecies tularensis and subspecies holarctica strains and correlates to their susceptibility to H(2)O(2)-induced killing

机译:图拉弗朗西斯菌和图拉菌亚种之间的铁含量不同,并且与铁对H(2)O(2)致死的敏感性相关

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摘要

Francisella tularensis, the causative agent of tularemia, is one of the most infectious bacterial pathogens known and is classified as a category A select agent and a facultative intracellular bacterium. Why F. tularensis subsp. tularensis causes a more severe form of tularemia than F. tularensis subsp. holarctica does is not known. In this study, we have identified prominent phenotypic differences between the subspecies, since we found that F. tularensis subsp. tularensis strains contained less iron than F. tularensis subsp. holarctica strains. Moreover, strain SCHU S4 of F. tularensis subsp. tularensis was less susceptible than FSC200 and the live vaccine strain (LVS) of F. tularensis subsp. holarctica to H(2)O(2)-induced killing. The activity of the H(2)O(2)-degrading enzyme catalase was similar between the strains, whereas the iron content affected their susceptibility to H(2)O(2), since iron starvation rendered F. tularensis subsp. holarctica strains more resistant to H(2)O(2). Complementing LVS with fupA, which encodes an important virulence factor that regulates iron uptake, reduced its iron content and increased the resistance to H(2)O(2)-mediated killing. By real-time PCR, it was demonstrated that FSC200 and LVS expressed higher levels of gene transcripts related to iron uptake and storage than SCHU S4 did, and this likely explained their high iron content. Together, the results suggest that F. tularensis subsp. tularensis strains have restricted iron uptake and storage, which is beneficial for their resistance to H(2)O(2)-induced killing. This may be an important factor for the higher virulence of this subspecies of F. tularensis, as reactive oxygen species, such as H(2)O(2), are important bactericidal components during tularemia.
机译:tularemia的病原体Francisella tularensis是已知的最具传染性的细菌病原体之一,被分类为A类选择剂和兼性细胞内细菌。为什么是F. tularensis亚种。 tularensis引起的tularemia形式比F. tularensis亚种更为严重。 holarctica不知道。在这项研究中,我们已经发现亚种之间显着的表型差异,因为我们发现了F. tularensis亚种。 tularensis菌株的铁含量低于F. tularensis亚种。嗜酸菌菌株。此外,图拉菌亚种的菌株SCHU S4。 tularensis不如FSC200和Fularus亚种的活疫苗株(LVS)易感。到H(2)O(2)诱导杀人。 H(2)O(2)降解酶过氧化氢酶的活性在两个菌株之间是相似的,而铁含量影响了它们对H(2)O(2)的敏感性,因为铁的饥饿导致图拉菌F. tularensis亚种。 holarctica菌株更耐H(2)O(2)。 LVS与fupA互补,fupA编码一种重要的毒力因子,可调节铁的吸收,降低其铁含量并增加对H(2)O(2)介导的杀伤力的抵抗力。通过实时PCR,证明与SCHU S4相比,FSC200和LVS表达了更高水平的与铁吸收和存储相关的基因转录本,这很可能解释了它们的高铁含量。在一起,结果表明F. tularensis亚种。 tularensis菌株限制了铁的吸收和存储,这对于它们对H(2)O(2)诱导的杀伤具有抵抗力是有益的。这可能是造成Tularensis亚种高毒力的重要因素,因为活性氧(例如H(2)O(2))是Tularemia期间的重要杀菌成分。

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