The PadR-like transcriptional regulator LftR ensures efficient invasion of Listeria monocytogenes into human host cells.
The PadR-like transcriptional regulator LftR ensures efficient invasion of Listeria monocytogenes into human host cells.
复制标题
PADR样转录调节剂LFTR确保有效侵入单核细胞增生李斯特氏菌中的人类宿主细胞。
DOI：
10.3389/fmicb.2015.00772
复制
发表时间：
2015
影响因子：
5.2
通讯作者：
Halbedel S
中科院分区：
文献类型：
--
作者：
Kaval KG;Hahn B;Tusamda N;Albrecht D;Halbedel S
单核细胞增生李斯特菌入侵人类宿主细胞需要特殊的表面分子附着和诱导吞噬。然而，有效的侵袭也依赖于具有管家功能的因素，如seca2依赖性的自溶素分泌，用于子细胞分裂后的分离。该途径的突变阻止肽聚糖跨壁降解，从而形成不能被吞噬的长细胞链。这种突变体的极端连锁表现为粗糙的集落表型。从一个转座子文库中分离到一个粗糙克隆，该克隆在未鉴定的lmo0720基因（lftS）上插入转座子，并在secA2基因上发生自发性点突变。我们分离了两个突变，并证明SecA2分子内调控2结构域的这个点突变足以使该蛋白失活。相反，lftS缺失不会导致ΔsecA2-like表型。lftS位于lftR （lmo0719）的操纵子中，编码一个类似padr的转录调控因子，lftR的缺失影响了生长、入侵和依赖光照的群体协调。lftS失活部分抑制了这些表型，表明LftR与lftS之间存在功能关系。然而，通过去除lftS， ΔlftR突变体的侵袭缺陷仅被轻微抑制。LftR调控lmo0979-0980 （lieAB）操纵子的表达，该操纵子编码一种假定的多药耐药转运体，在LftR缺失的情况下，lieAB的转录被强烈上调。在ΔlftR背景中删除lieAB可以恢复野生型入侵水平。因此，我们得出结论，liab操纵子的严格转录抑制对有效的李氏宿主细胞侵袭至关重要。
Invasion of the bacterial pathogen Listeria monocytogenes into human host cells requires specialized surface molecules for attachment and induction of phagocytosis. However, efficient invasion is also dependent on factors with house-keeping functions, such as SecA2-dependent secretion of autolysins for post-divisional segregation of daughter cells. Mutations in this pathway prevent degradation of peptidoglycan cross-walls, so that long cell chains are formed that cannot be phagocytosed. The extreme chaining of such mutants manifests as rough colony phenotype. One rough clone was isolated from a transposon library with a transposon insertion in the uncharacterized lmo0720 gene (lftS) together with a spontaneous point mutation in the secA2 gene. We separated both mutations and demonstrated that this point mutation in the intramolecular regulator 2 domain of SecA2 was sufficient to inactivate the protein. In contrast, lftS deletion did not cause a ΔsecA2-like phenotype. lftS is located in an operon with lftR (lmo0719), encoding a PadR-like transcriptional regulator, and lftR deletion affected growth, invasion and day-light dependent coordination of swarming. Inactivation of lftS partially suppressed these phenotypes, suggesting a functional relationship between LftR and LftS. However, the invasion defect of the ΔlftR mutant was only marginally suppressed by lftS removal. LftR regulates expression of the lmo0979–0980 (lieAB) operon, encoding a putative multidrug resistance transporter and lieAB transcription was strongly upregulated in the absence of LftR. Deletion of lieAB in the ΔlftR background restores wild type-like invasion levels. Hence, we conclude that tight transcriptional repression of the lieAB operon is essential for efficient listerial host cell invasion.