Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization
Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization
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DOI：
10.15252/embr.201744880
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发表时间：
2018-05-01
期刊：
影响因子：
7.7
通讯作者：
Ferrandon, Dominique
中科院分区：
文献类型：
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作者：
Haller, Samantha;Franchet, Adrien;Ferrandon, Dominique
当黑腹果蝇以铜绿假单胞菌为食时，一些细菌穿过肠屏障并最终在血腔中增殖。这一过程受到血细胞吞噬作用的限制。铜绿假单胞菌需要群体感应调节剂RhlR来逃避果蝇的细胞免疫应答。RhlI合成激活RhlR的自诱导物信号。在这里，我们表明，rhlI突变体比rhlR突变体的毒力出乎意料，无论是在苍蝇和线虫肠道感染模型，表明RhlR具有RhlI独立的功能。我们还报道了RhlR保护铜绿假单胞菌免受果蝇含硫酯蛋白4（Tep4）介导的调理作用。RhlR突变体细菌显示出更高水平的Tep4介导的调理作用，相比rhlI突变体，这防止了果蝇血腔中的致命菌血症。相比之下，在感染的脓毒症模型中，其中细菌被直接引入血腔，Tep4突变果蝇对野生型铜绿假单胞菌更具抗性，但对rhlR突变体没有抗性。因此，根据感染途径，Tep4调理素可以对宿主防御起保护作用，也可以对宿主防御有害。
When Drosophila melanogaster feeds on Pseudomonas aeruginosa, some bacteria cross the intestinal barrier and eventually proliferate in the hemocoel. This process is limited by hemocytes through phagocytosis. P. aeruginosa requires the quorum-sensing regulator RhlR to elude the cellular immune response of the fly. RhlI synthesizes the autoinducer signal that activates RhlR. Here, we show that rhlI mutants are unexpectedly more virulent than rhlR mutants, both in fly and in nematode intestinal infection models, suggesting that RhlR has RhlI-independent functions. We also report that RhlR protects P. aeruginosa from opsonization mediated by the Drosophila thioester-containing protein 4 (Tep4). RhlR mutant bacteria show higher levels of Tep4-mediated opsonization, as compared to rhlI mutants, which prevents lethal bacteremia in the Drosophila hemocoel. In contrast, in a septic model of infection, in which bacteria are introduced directly into the hemocoel, Tep4 mutant flies are more resistant to wild-type P. aeruginosa, but not to the rhlR mutant. Thus, depending on the infection route, the Tep4 opsonin can either be protective or detrimental to host defense.