The Transcriptional Regulator SpxA1 Influences the Morphology and Virulence of Listeria monocytogenes.
The Transcriptional Regulator SpxA1 Influences the Morphology and Virulence of Listeria monocytogenes.
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转录调节因子 SpxA1 影响单核细胞增生李斯特氏菌的形态和毒力。
DOI：
10.1128/iai.00211-22
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发表时间：
2022-10-20
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
单核增生李斯特菌是一种革兰氏阳性兼性厌氧菌，是研究哺乳动物宿主感染过程中发生的调节变化的良好模型病原体。SpxA1是一种广泛保守的转录调节因子，可诱导单核增生乳杆菌中过氧化物解毒基因的表达，因此是需氧生长所必需的。SpxA1也是单核增生乳杆菌毒力所必需的，尽管在这种情况下重要的SpxA1依赖基因仍有待鉴定。在这里，我们试图研究SpxA1在感染的组织培养模型中的作用，并令人惊讶地发现ΔspxA1细胞在宿主细胞质中生长时显着延长。定量显微镜显示，在富培养基中，ΔspxA1细胞在指数期早期也在细胞外形成细长的细丝。扫描电镜和透射电镜分析发现，这种形态表型的可能原因是异常放置的分裂间隔定位在细胞中点外。全细胞裂解物的定量质谱分析鉴定了spxa1依赖性蛋白丰度的变化，包括在ΔspxA1突变体中大量的运动性和鞭毛蛋白被耗尽。因此，我们发现丝化和缺乏运动性都导致巨噬细胞对ΔspxA1细胞的吞噬能力下降。总之，我们确定了SpxA1在调节细胞伸长和运动方面的新作用，这两者都影响单核增生乳杆菌的毒力。
Listeria monocytogenes is a Gram-positive facultative anaerobe and an excellent model pathogen for investigating regulatory changes that occur during infection of a mammalian host. SpxA1 is a widely conserved transcriptional regulator that induces expression of peroxide-detoxifying genes in L. monocytogenes and is thus required for aerobic growth. SpxA1 is also required for L. monocytogenes virulence, although the SpxA1-dependent genes important in this context remain to be identified. Here, we sought to investigate the role of SpxA1 in a tissue culture model of infection and made the surprising discovery that ΔspxA1 cells are dramatically elongated during growth in the host cytosol. Quantitative microscopy revealed that ΔspxA1 cells also form elongated filaments extracellularly during early exponential phase in rich medium. Scanning and transmission electron microscopy analysis found that the likely cause of this morphological phenotype is aberrantly placed division septa localized outside cell midpoints. Quantitative mass spectrometry of whole-cell lysates identified SpxA1-dependent changes in protein abundance, including a significant number of motility and flagellar proteins that were depleted in the ΔspxA1 mutant. Accordingly, we found that both the filamentation and the lack of motility contributed to decreased phagocytosis of ΔspxA1 cells by macrophages. Overall, we identify a novel role for SpxA1 in regulating cell elongation and motility, both of which impact L. monocytogenes virulence.
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影响因子：
6.7
作者：
Frirdich E;Biboy J;Adams C;Lee J;Ellermeier J;Gielda LD;Dirita VJ;Girardin SE;Vollmer W;Gaynor EC
通讯作者：
Gaynor EC
影响因子：
6.4
作者：
McFarland AP;Burke TP;Carletti AA;Glover RC;Tabakh H;Welch MD;Woodward JJ
通讯作者：
Woodward JJ
影响因子：
3.1
作者：
KUHN, M;GOEBEL, W
通讯作者：
GOEBEL, W
影响因子：
2.9
作者：
PRENDERGAST, FG;HAUGLAND, RP;CALLAHAN, PJ
通讯作者：
CALLAHAN, PJ
影响因子：
64.5
作者：
Bartlett TM;Bratton BP;Duvshani A;Miguel A;Sheng Y;Martin NR;Nguyen JP;Persat A;Desmarais SM;VanNieuwenhze MS;Huang KC;Zhu J;Shaevitz JW;Gitai Z
通讯作者：
Gitai Z