The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction.
The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction.
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DOI：
10.1038/ncomms11951
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发表时间：
2016-06-15
影响因子：
16.6
通讯作者：
Skaar EP
中科院分区：
文献类型：
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作者：
Wakeman CA;Moore JL;Noto MJ;Zhang Y;Singleton MD;Prentice BM;Gilston BA;Doster RS;Gaddy JA;Chazin WJ;Caprioli RM;Skaar EP
微生物形成含有分化细胞群的生物膜。为了确定驱动分化的因素，我们在此使用成像质谱法可视化铜绿假单胞菌生物膜内的蛋白质和金属分布。这些体外实验揭示了差异蛋白质分布和金属丰度之间的相关性。值得注意的是，锌和锰耗尽部分的生物膜抑制生产的抗葡萄球菌分子。暴露于钙卫蛋白（一种已知在感染灶处螯合金属离子的宿主蛋白质）重现了生物膜金属耗尽部分内发生的反应，并促进了铜绿假单胞菌和金黄色葡萄球菌之间的相互作用。与这些结果一致，钙卫蛋白的存在促进鼠肺的共定殖，并且发现多微生物群落共存于囊性纤维化肺外植体的钙卫蛋白富集的气隙中。这些发现表明，金属波动是微生物群落结构的驱动力，由于铜绿假单胞菌和S.金黄色葡萄球菌合并感染。 铜绿假单胞菌和金黄色葡萄球菌的合并感染在囊性纤维化患者中很常见。在这里，作者表明，由宿主蛋白钙卫蛋白诱导的金属耗竭通过抑制铜绿假单胞菌产生抗葡萄球菌分子来促进两种病原体的共存。
Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we herein visualize protein and metal distributions within Pseudomonas aeruginosa biofilms using imaging mass spectrometry. These in vitro experiments reveal correlations between differential protein distribution and metal abundance. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections. Co-infections with Pseudomonas aeruginosa and Staphylococcus aureus are common in cystic fibrosis patients. Here, the authors show that metal depletion induced by a host protein, calprotectin, promotes co-existence of both pathogens by inhibiting production of anti-staphylococcal molecules by P. aeruginosa.