Structure of the Type VI Effector-Immunity Complex (Tae4-Tai4) Provides Novel Insights into the Inhibition Mechanism of the Effector by Its Immunity Protein*

Zhang, Heng; Gao, Zengqiang; Wang, Wenjia; Liu, Guangfeng; Xu, Jianhua; Su, Xiao‐Dong; Dong, Yuhui

doi:10.1074/jbc.m112.434357

Cited by 60 publications

(90 citation statements)

References 38 publications

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“…For example, we found that E. cloacae is not killed by the SPI-6 attack. This result is in agreement with the fact that the genome of E. cloacae encodes a Tai4 immunity protein that has been shown to bind and inhibit S. Typhimurium Tae4 activity (35,57). In our study, we found that the ability of S. Typhimurium to kill E. coli was strain-dependent.…”

Section: Discussionsupporting

confidence: 80%

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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Section: Discussionsupporting

confidence: 80%

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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“…Given the two oligomeric forms of VgrG-3C/TsaB as observed through size exclusion chromatography using the same preincubation conditions, we hypothesize that the incomplete inhibition of PGdegrading activity may arise from unsaturation of VgrG-3C. Zhang et al (19) describe a similar interaction between Tae4 and Tai4, a toxin-antitoxin pair of the Enterobacter cloacae T6SS, in which an antitoxin dimer is required to inactivate the Tae4 toxin. These results indicate that TsaB has a direct inhibitory effect on the lytic activity of VgrG-3C.…”

Section: Delivery Of Vgrg-3 or Vgrg-3c To The Periplasm Is Toxic To Ementioning

confidence: 98%

Lytic Activity of the Vibrio cholerae Type VI Secretion Toxin VgrG-3 Is Inhibited by the Antitoxin TsaB

Brooks

Unterweger

Bachmann

et al. 2013

Journal of Biological Chemistry

152

191

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Background:The type VI secretion system provides Gram-negative bacteria with a competitive advantage. Results: The V. cholerae T6SS component VgrG-3 has lysozyme-like activity that is inhibited by the product of the downstream gene tsaB. Conclusion: VgrG-3 and TsaB are a toxin-antitoxin complex of the V. cholerae T6SS. Significance: A T6SS effector is characterized along with its cognate antitoxin.

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“…1A) (41). The gene cluster encodes all the genes required to assemble a functional secretion apparatus, as well as three effectors (STM0277, tae4; STM0291 and STM0292, rhs) and their cognate immunity proteins (STM0278, tai4; STM0291b and STM0293, rhsI) (42)(43)(44)(45). tae4 encodes a toxin with peptidoglycan hydrolase activity, whereas the Rhs C-terminal domains carry putative nu- Salmonella Typhimurium SPI-6-encoded T6SS gene cluster.…”

mentioning

confidence: 99%

“…clease activities (42)(43)(44)(45). The upstream operon (STM0266-STM0271) consists of a number of genes encoding machine subunits and two genes of unknown function.…”

mentioning

confidence: 99%

H-NS Silencing of the Salmonella Pathogenicity Island 6-Encoded Type VI Secretion System Limits Salmonella enterica Serovar Typhimurium Interbacterial Killing

et al. 2015

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The secretion of bacterial toxin proteins is achieved by dedicated machineries called secretion systems. The type VI secretion system (T6SS) is a widespread versatile machine used for the delivery of protein toxins to both prokaryotic and eukaryotic cells. In Salmonella enterica serovar Typhimurium, the expression of the T6SS genes is activated during macrophage or mouse infection. Here, we show that the T6SS gene cluster is silenced by the histone-like nucleoid structuring H-NS protein using a combination of reporter fusions, electrophoretic mobility shift assays, DNase footprinting, and fluorescence microscopy. We further demonstrate that derepression of the S. Typhimurium T6SS genes induces T6SS-dependent intoxication of competing bacteria. Our results suggest that relieving T6SS H-NS silencing may be used as a sense-and-kill mechanism that will help S. Typhimurium to homogenize and synchronize the microbial population to gain efficiency during infection. During the course of infection, bacteria produce and secrete bacterial toxins. Secretion of these toxin proteins is achieved by dedicated, specialized machineries called secretion systems. The type VI secretion system (T6SS) is required for the virulence of several Gram-negative pathogens. In Vibrio cholerae, the T6SS translocates VgrG1, a toxin that carries a domain responsible for actin cross-linking in eukaryotic cells (1-4). However, the role of the T6SS is not limited to virulence toward eukaryotes; an increasing number of reports demonstrate that the T6SS is also involved in interbacterial intoxication (5-10). With bacteriocins and contact-dependent inhibition (CDI), the T6SS is therefore involved in shaping bacterial communities (11-14) by delivering antibacterial toxins, including murein hydrolases, DNases, and phospholipases, directly into the target recipient bacterial cell (5, 6, 15; for recent reviews see references 14, 16 and 17). The attacker cell is protected from these toxins by the coproduction of cognate proteins that confer immunity (15, 18). The T6SS therefore confers a growth advantage to bacteria in mixed cultures and has been suggested to be important in environmental niches where bacterial competition for nutrients is critical for survival or for the uptake of DNA for transformation and acquisition of new traits (14, 19). However, while the role of the T6SS in interbacterial competition has been evidenced and characterized under laboratory conditions, its role in shaping bacterial communities of the microbiota is not yet clearly elucidated.At the molecular level, the T6SS is assembled from 13 proteins, called core components, that form a transenvelope apparatus anchoring a cytoplasmic tubular structure to the membrane (20-24). Based on structural homologies with bacteriophage tail components, this tubular structure has been proposed to be constituted of an inner tube assembled by stacked hexameric rings of the Hcp protein, resembling the tail tube of bacteriophages, tipped by the VgrG protein (21,(25)(26)(27)). The current model descr...

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Structure of the Type VI Effector-Immunity Complex (Tae4-Tai4) Provides Novel Insights into the Inhibition Mechanism of the Effector by Its Immunity Protein*

Cited by 60 publications

References 38 publications

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

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

Lytic Activity of the Vibrio cholerae Type VI Secretion Toxin VgrG-3 Is Inhibited by the Antitoxin TsaB

H-NS Silencing of the Salmonella Pathogenicity Island 6-Encoded Type VI Secretion System Limits Salmonella enterica Serovar Typhimurium Interbacterial Killing

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