Cooperation between LepA and PlcH Contributes to the In Vivo Virulence and Growth of Pseudomonas aeruginosa in Mice

Cooperation between LepA and PlcH Contributes to the In Vivo Virulence and Growth of Pseudomonas aeruginosa in Mice
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DOI:
10.1128/iai.01053-10
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发表时间:
2011-01-01
影响因子:
3.1
通讯作者:
Kuwano, Koichi
Kuwano, Koichi
中科院分区:
医学2区
文献类型:
--
作者:
Kida, Yutaka;Shimizu, Takashi;Kuwano, Koichi

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铜绿假单胞菌衍生的大胞外蛋白酶 (LepA) 和溶血磷脂酶 C (PlcH) 被认为在该生物体的致病性中发挥重要作用。尽管细菌生长似乎与毒力密切相关,但人们对 LepA 和 PlcH 是否参与铜绿假单胞菌的生长和毒力知之甚少。在这项研究中,我们使用野生型菌株和突变体研究了 LepA 和 PlcH 是否有助于铜绿假单胞菌的毒力和生长。在含有血清白蛋白或血红蛋白作为唯一碳源和氮源的基本培养基中,同基因lepA单突变体的生长速率低于野生型菌株。此外,在以红细胞作为唯一生长营养源的基本培养基中,lepA plcH双突变体的生长速率与野生型菌株相比大大降低。因此,这些结果表明LepA和PlcH之间的合作将有助于利用红细胞作为铜绿假单胞菌生长的唯一营养源。此外,小鼠感染实验表明,lepA和plcH单突变株毒力减弱,腹腔灌洗液和全血标本中突变株数量低于野生型菌株数量。特别是lepA plcH双突变体的毒力和生长速度明显低于野生型菌株。总的来说,这些结果表明 LepA 和 PlcH 有助于铜绿假单胞菌的体内毒力和生长。
Pseudomonas aeruginosa-derived large extracellular protease (LepA) and hemolytic phospholipase C (PlcH) are considered to play an important role in the pathogenicity of this organism. Although bacterial growth appears to be closely related to virulence, little is known about whether LepA and PlcH participate in the growth and virulence of P. aeruginosa. In this study, we investigated whether LepA and PlcH contribute to the virulence and growth of P. aeruginosa using a wild-type strain and mutants. The growth rate of the isogenic lepA single mutant was lower than that of the wild-type strain in a minimal medium containing serum albumin or hemoglobin as the sole carbon and nitrogen source. Furthermore, the growth rate of the lepA plcH double mutant decreased greatly compared with that of the wild-type strain in a minimal medium containing erythrocytes as a sole nutrient source for growth. Thus, these results indicate that cooperation between LepA and PlcH would contribute to the utilization of erythrocytes as a sole nutrient source for the growth of P. aeruginosa. In addition, mouse infection experiments demonstrated that the virulence of the lepA and plcH single mutants was attenuated, and the numbers of the mutants were lower than the numbers of the wild-type strain in peritoneal lavage fluid and whole-blood specimens. In particular, the virulence and growth rate of the lepA plcH double mutant were markedly lower than those of the wild-type strain. Collectively, these results suggest that LepA and PlcH contribute to the in vivo virulence and growth of P. aeruginosa.