Hcp Family Proteins Secreted via the Type VI Secretion System Coordinately Regulate Escherichia coli K1 Interaction with Human Brain Microvascular Endothelial Cells

Zhou, Yan; Tao, Jing; Yu, Hao; Ni, Jinjing; Zeng, Lingbing; Teng, Qihui; Kim, Kwang Sik; Zhao, Guo Ping; Guo, Xin; Yao, Yufeng

doi:10.1128/iai.05994-11

Cited by 106 publications

(118 citation statements)

References 51 publications

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“…de Pace et al (14) found that the mutants of T6SS core genes (clpV and hcp) of APEC strain SEPT362 displayed decreased adherence and actin rearrangement on epithelial cells. A similar result was revealed by research on the Hcp mutant of the neonatal meningitis E. coli (NMEC) strain RS218 (15). However, the means by which T6SSs contribute to virulence remain unknown, and the mechanisms warrant further investigation.…”

supporting

confidence: 54%

Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

Bao

Sun

et al. 2014

Infect Immun

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Type VI secretion systems (T6SSs) are involved in the pathogenicity of several Gram-negative bacteria. The VgrG protein, a core component and effector of T6SS, has been demonstrated to perform diverse functions. The N-terminal domain of VgrG protein is a homologue of tail fiber protein gp27 of phage T4, which performs a receptor binding function and determines the host specificity. Based on sequence analysis, we found that two putative T6SS loci exist in the genome of the avian pathogenic Escherichia coli (APEC) strain TW-XM. To assess the contribution of these two T6SSs to TW-XM pathogenesis, the crucial clpV clusters of these two T6SS loci and their vgrG genes were deleted to generate a series of mutants. Consequently, T6SS1-associated mutants presented diminished adherence to and invasion of several host cell lines cultured in vitro, decreased pathogenicity in duck and mouse infection models in vivo, and decreased biofilm formation and bacterial competitive advantage. In contrast, T6SS2-associated mutants presented a significant decrease only in the adherence to and invasion of mouse brain microvascular endothelial cell (BMEC) line bEnd.3 and brain tissue of the duck infection model. These results suggested that T6SS1 was involved in the proliferation of APEC in systemic infection, whereas VgrG-T6SS2 was responsible only for cerebral infection. Further study demonstrated that VgrG-T6SS2 was able to bind to the surface of bEnd.3 cells, whereas it did not bind to DF-1 (chicken embryo fibroblast) cells, which further proved the interaction of VgrG-T6SS2 with the surface of BMECs.

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supporting

confidence: 54%

Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

Bao

Sun

et al. 2014

Infect Immun

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“…These differences might explain the specificity of interaction with different effectors. Interestingly, Zhou et al previously reported that Hcp1 and Hcp2 of E. coli K1 have differential roles in binding and invading human endothelial cells and in actin cytoskeleton rearrangement, respectively, suggesting a similar mechanism of binding to different effectors (54). Therefore, this mechanism of specificity could be common among T6SSs.…”

Section: Discussionmentioning

confidence: 99%

Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut

Sana

Flaugnatti

Lugo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

278

292

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The mammalian gastrointestinal tract is colonized by a high-density polymicrobial community where bacteria compete for niches and resources. One key competition strategy includes cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), a multiprotein needle-like apparatus that injects effector proteins into prokaryotic and/or eukaryotic target cells. However, the contribution of T6SS antibacterial activity during pathogen invasion of the gut has not been demonstrated. We report that successful establishment in the gut by the enteropathogenic bacterium Salmonella enterica serovar Typhimurium requires a T6SS encoded within Salmonella pathogenicity island-6 (SPI-6). In an in vitro setting, we demonstrate that bile salts increase SPI-6 antibacterial activity and that S. Typhimurium kills commensal bacteria in a T6SS-dependent manner. Furthermore, we provide evidence that one of the two T6SS nanotube subunits, Hcp1, is required for killing Klebsiella oxytoca in vitro and that this activity is mediated by the specific interaction of Hcp1 with the antibacterial amidase Tae4. Finally, we show that K. oxytoca is killed in the host gut in an Hcp1-dependent manner and that the T6SS antibacterial activity is essential for Salmonella to establish infection within the host gut. Our findings provide an example of pathogen T6SS-dependent killing of commensal bacteria as a mechanism to successfully colonize the host gut.

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“…ClpV is an ATPase that forms oligomeric complexes to energize the system for the secretion of effector proteins, while Vgr and Hcp-2 are effector proteins (1,(12)(13)(14)17). To understand which of these proteins affected the expression of the flagellar genes at the level of transcription, we constructed three mutants (CF74⌬clpV, CF74 ⌬hcp-2, and CF74⌬vgr) and complemented strains [CF74⌬clpV (pBAD24-clpV), CF74⌬hcp-2(pBAD24-hcp-2), and CF74⌬vgr (pBAD24-vgr)], in which the expression of the six flagellar genes were measured by qRT-PCR analysis.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that the T6SS contributes to the virulence development of various pathogens and is often activated upon contact with target cells for the secretion of effector proteins (1)(2)(3)(4)(5)(6)(7)(14)(15)(16)(17). The expression and assembly of the T6SS are tightly controlled at both the transcriptional and posttranscriptional levels (12,13,18).…”

mentioning

confidence: 99%

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The Type VI Secretion System Modulates Flagellar Gene Expression and Secretion in Citrobacter freundii and Contributes to Adhesion and Cytotoxicity to Host Cells

et al. 2015

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eThe type VI secretion system (T6SS) as a virulence factor-releasing system contributes to virulence development of various pathogens and is often activated upon contact with target cells. Citrobacter freundii strain CF74 has a complete T6SS genomic island (GI) that contains clpV, hcp-2, and vgr T6SS genes. We constructed clpV, hcp-2, vgr, and T6SS GI deletion mutants in CF74 and analyzed their effects on the transcriptome overall and, specifically, on the flagellar system at the levels of transcription and translation. Deletion of the T6SS GI affected the transcription of 84 genes, with 15 and 69 genes exhibiting higher and lower levels of transcription, respectively. Members of the cell motility class of downregulated genes of the CF74⌬T6SS mutant were mainly flagellar genes, including effector proteins, chaperones, and regulators. Moreover, the production and secretion of FliC were also decreased in clpV, hcp-2, vgr, or T6SS GI deletion mutants in CF74 and were restored upon complementation. In swimming motility assays, the mutant strains were found to be less motile than the wild type, and motility was restored by complementation. The mutant strains were defective in adhesion to HEp-2 cells and were restored partially upon complementation. Further, the CF74⌬T6SS, CF74⌬clpV, and CF74⌬hcp-2 mutants induced lower cytotoxicity to HEp-2 cells than the wild type. These results suggested that the T6SS GI in CF74 regulates the flagellar system, enhances motility, is involved in adherence to host cells, and induces cytotoxicity to host cells. Thus, the T6SS plays a wide-ranging role in C. freundii.

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Hcp Family Proteins Secreted via the Type VI Secretion System Coordinately Regulate Escherichia coli K1 Interaction with Human Brain Microvascular Endothelial Cells

Cited by 106 publications

References 51 publications

Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

Two Functional Type VI Secretion Systems in Avian Pathogenic Escherichia coli Are Involved in Different Pathogenic Pathways

Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut

The Type VI Secretion System Modulates Flagellar Gene Expression and Secretion in Citrobacter freundii and Contributes to Adhesion and Cytotoxicity to Host Cells

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