Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
mSphere. 2024 May 29;9(5):e0006024. doi: 10.1128/msphere.00060-24. Epub 2024 Apr 22.
is an emerging pathogen isolated in healthcare-associated infections. A major virulence factor of this bacterium is the type VI secretion system (T6SS). The genome of harbors two T6SS gene clusters (T6SS-1 and T6SS-2), and the functional characterization of both systems showed that these two T6SSs are not expressed under the same conditions. Here, we report that the major histone-like protein HU positively regulates the expression of both T6SSs and, therefore, the function that each T6SS exerts in . Single deletions of the genes encoding the HU subunits ( and ) decreased mRNA levels of both T6SS. In contrast, the double mutant dramatically affected the T6SS expression, diminishing its transcription. The direct binding of HU to the promoter regions of T6SS-1 and T6SS-2 was confirmed by electrophoretic mobility shift assay. In addition, single and double mutations in the genes affected the ability of inter-bacterial killing, biofilm formation, adherence to epithelial cells, and intestinal colonization, but these phenotypes were restored when such mutants were -complemented. Our data broaden our understanding of the regulation of HU-mediated T6SS in these pathogenic bacteria.
T6SS is a nanomachine that functions as a weapon of bacterial destruction crucial for successful colonization in a specific niche. expresses two T6SSs required for bacterial competition, adherence, biofilm formation, and intestinal colonization. Expression of T6SS genes in pathogenic bacteria is controlled by multiple regulatory systems, including two-component systems, global regulators, and nucleoid proteins. Here, we reported that the HU nucleoid protein directly activates both T6SSs in , affecting the T6SS-related phenotypes. Our data describe HU as a new regulator involved in the transcriptional regulation of T6SS and its impact on pathogenesis.
是一种在与医疗保健相关的感染中分离出来的新兴病原体。该细菌的一个主要毒力因子是 VI 型分泌系统（T6SS）。 基因组含有两个 T6SS 基因簇（T6SS-1 和 T6SS-2），对这两个系统的功能特征进行了描述，表明这两种 T6SS 并非在相同条件下表达。在这里，我们报告说主要组蛋白样蛋白 HU 正向调节两个 T6SS 的表达，因此，每个 T6SS 在 中发挥的功能。编码 HU 亚基（ 和 ）的基因的单个缺失降低了两个 T6SS 的 mRNA 水平。相比之下， 双突变体显着影响 T6SS 的表达，使其转录减少。通过电泳迁移率变动分析证实了 HU 直接与 T6SS-1 和 T6SS-2 的启动子区域结合。此外， 基因的单个和双突变影响了细菌间杀伤、生物膜形成、上皮细胞粘附和肠道定植的能力，但当这些突变体被 -互补时，这些表型得到恢复。我们的数据拓宽了我们对 HU 介导的 T6SS 在这些病原菌中调节的理解。
T6SS 是一种纳米机器，作为细菌破坏的武器，对于在特定小生境中成功定植至关重要。 表达两种 T6SS，这对于细菌竞争、粘附、生物膜形成和肠道定植是必需的。病原菌中 T6SS 基因的表达受多种调控系统控制，包括双组分系统、全局调控因子和核蛋白。在这里，我们报告说 HU 核蛋白直接激活了 中的两个 T6SS，影响了与 T6SS 相关的表型。我们的数据将 HU 描述为一个新的调节剂，参与 T6SS 的转录调控及其对 发病机制的影响。
