<i>Vibrio cholerae</i>
            type 6 secretion system effector trafficking in target bacterial cells

Ho, Brian T.; Fu, Yang; Dong, Tao; Mekalanos, John J.

doi:10.1073/pnas.1711219114

Cited by 65 publications

(72 citation statements)

References 40 publications

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“…First, the development of cholera in humans is a complex, multifactorial process that can be reproduced in zebrafish very easily. Second, the animal models typically used in cholera research are not native cholera hosts, and the mechanisms of their colonization may be different; however, zebrafish naturally host V. cholerae (31,32). Third, V. cholerae colonization in other animal models requires the disruption or absence of intestinal microbiota, whereas V. cholerae colonization in zebrafish occurs in the presence of intact intestinal microbiota (15,17).…”

Section: Discussionmentioning

confidence: 99%

Glucose Metabolism by Escherichia coli Inhibits Vibrio cholerae Intestinal Colonization of Zebrafish

et al. 2018

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The Vibrio cholerae O1 serogroup is responsible for pandemic cholera and is divided into the classical and El Tor biotypes. Classical V. cholerae produces acid when using glucose as a carbon source, whereas El Tor V. cholerae produces the neutral product acetoin when using glucose as a carbon source. An earlier study demonstrated that Escherichia coli strains that metabolize glucose to acidic byproducts drastically reduced the survival of V. cholerae strains in vitro. In the present study, zebrafish were fed 1% glucose and either inoculated with single V. cholerae or E. coli strains or coinfected with both V. cholerae and E. coli. A significant decrease in classical biotype colonization was observed after glucose feeding due to acid production in the zebrafish intestine. El Tor colonization was unaffected by glucose alone. However, the El Tor strain exhibited significantly lower colonization of the zebrafish when either of the acid-producing E. coli strains was coinoculated in the presence of glucose. An E. coli sugar transport mutant had no effect on V. cholerae colonization even in presence of glucose. Glucose and E. coli produced a prophylactic effect on El Tor colonization in zebrafish when E. coli was inoculated before V. cholerae infection. Thus, the probiotic feeding of E. coli inhibits V. cholerae colonization in a natural host. This suggests that a similar inhibitory effect could be seen in cholera patients, especially if a glucose-based oral rehydration solution (ORS) is administered in combination with probiotic E. coli during cholera treatment. FIG 2 Effect of glucose feeding on classical and El Tor V. cholerae colonization of zebrafish intestine. Zebrafish were fed 1% glucose for 12 h, and ϳ5 ϫ 10 6 CFU/ml of either V. cholerae O395 or N16961 was inoculated in zebrafish. V. cholerae levels were determined by plating of serial dilutions of the intestinal homogenates. *, P ϭ 0.005. Probiotic Inhibition of V. cholerae Colonization Infection and Immunity December 2018 Volume 86 Issue 12 e00486-18 iai.asm.org 3 on July 5, 2020 by guest http://iai.asm.org/ Downloaded from FIG 3 Effect of E. coli strains plus glucose on V. cholerae colonization of zebrafish intestine. Zebrafish were fed 1% glucose for 12 h, and ϳ5 ϫ 10 6 CFU/ml of E. coli 40 and N was coinoculated with ϳ5 ϫ 10 6 CFU/ml of either V. cholerae O395 or N16961. (A) Coinfection of E. coli with classical V. cholerae strain O395. (B) Coinfection of E. coli with El Tor V. cholerae strain N16961. V. cholerae levels were determined by plating of serial dilutions of the intestinal homogenates. Horizontal bars indicate the mean colonization level for each group, and individual symbols indicate the results for individual fish. ***, P Ͻ 0.0001; **, P Ͻ 0.001; NS, nonsignificant differences.Probiotic Inhibition of V. cholerae Colonization Infection and Immunity December 2018 Volume 86 Issue 12 e00486-18 iai.asm.org 5 on July 5, 2020 by guest http://iai.asm.org/ Downloaded from FIG 5 Effect of E. coli feeding plus glucose before V. cholerae infection on N16...

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Section: Discussionmentioning

confidence: 99%

Glucose Metabolism by Escherichia coli Inhibits Vibrio cholerae Intestinal Colonization of Zebrafish

et al. 2018

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“…This effect could be observed because TleV1 has a catalytic activity when present in both the cytoplasm and the periplasm. Alternatively, TleV1 could have a cryptic signal that exports the wild-type protein to the periplasm even in the absence of an exogenous signal, as proposed for other T6SS effectors [51]. Expression of the predicted immunity gene upstream of TleV1 was able to neutralize the toxicity of the effector in both E. coli and V. cholerae cells.…”

Section: Discovery Characterization and Validation Of Novel T6ss Gementioning

confidence: 97%

Analysis of Vibrio cholerae genomes identifies new type VI secretion system gene clusters

Crisan¹,

Chande²,

Williams³

et al. 2019

Genome Biol

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Background Like many bacteria, Vibrio cholerae deploys a harpoon-like type VI secretion system (T6SS) to compete against other microbes in environmental and host settings. The T6SS punctures adjacent cells and delivers toxic effector proteins that are harmless to bacteria carrying cognate immunity factors. Only four effector/immunity pairs encoded on one large and three auxiliary gene clusters have been characterized from largely clonal, patient-derived strains of V. cholerae . Results We sequence two dozen V. cholerae strain genomes from diverse sources and develop a novel and adaptable bioinformatics tool based on hidden Markov models. We identify two new T6SS auxiliary gene clusters and describe Aux 5 here. Four Aux 5 loci are present in the host strain, each with an atypical effector/immunity gene organization. Structural prediction of the putative effector indicates it is a lipase, which we name TleV1 (type VI lipase effector Vibrio ). Ectopic TleV1 expression induces toxicity in Escherichia coli , which is rescued by co-expression of the TliV1a immunity factor. A clinical V. cholerae reference strain expressing the Aux 5 cluster uses TleV1 to lyse its parental strain upon contact via its T6SS but is unable to kill parental cells expressing the TliV1a immunity factor. Conclusion We develop a novel bioinformatics method and identify new T6SS gene clusters in V. cholerae . We also show the TleV1 toxin is delivered in a T6SS manner by V. cholerae and can lyse other bacterial cells. Our web-based tool can be modified to identify additional novel T6SS genomic loci in diverse bacterial species. Electronic supplementary material The online version of this article (10.1186/s13059-019-1765-5) contains supplementary material, which is available to authorized users.

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“…Among the protein secretion systems that facilitate these interactions, the predominant function of the type VI secretion system (T6SS) 3 is to mediate antagonistic interactions between contacting Gram-negative bacteria (1). The T6SS is a membrane-embedded protein complex that resembles the tail component of contractile bacteriophage (2).…”

mentioning

confidence: 99%

“…The T6SS is a membrane-embedded protein complex that resembles the tail component of contractile bacteriophage (2). Through cycles of extension and contraction, this pathway delivers effector proteins from the cytoplasm of a donor bacterium directly into the periplasm or cytoplasm of a recipient bacterium (3,4). Used by both pathogenic and commensal bacteria of eukaryotes, the T6SS mediates a complex interplay of bacterial cell-cell interactions between beneficial and disease-causing bacteria (5)(6)(7)(8)(9).…”

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confidence: 99%

Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system

Tang

Bullen

Ahmad

et al. 2018

Journal of Biological Chemistry

100

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The bacterial type VI secretion system (T6SS) mediates antagonistic cell-cell interactions between competing Gram-negative bacteria. In plant-beneficial bacteria, this pathway has been shown to suppress the growth of bacterial pathogens; however, the identification and mode of action of T6SS effector proteins that mediate this protective effect remain poorly defined. Here, we identify two previously uncharacterized effectors required for interbacterial antagonism by the plant commensal bacterium Pseudomonas protegens. Consistent with the established effector-immunity paradigm for antibacterial T6SS substrates, the toxic activities of these effectors are neutralized by adjacently encoded cognate immunity determinants. Although one of these effectors, RhsA, belongs to the family of DNase enzymes, the activity of the other was not apparent from its sequence. To determine the mechanism of toxicity of this latter effector, we determined its 1.3 Å crystal structure in complex with its immunity protein and found that it resembles NAD(P) ؉ -degrading enzymes. In line with this structural similarity, biochemical characterization of this effector, termed Tne2 (Type VI secretion NADase effector family 2), demonstrates that it possesses potent NAD(P) ؉ hydrolase activity. Tne2 is the founding member of a widespread family of interbacterial NADases predicted to transit not only the Gram-negative T6SS but also the Gram-positive type VII secretion system, a pathway recently implicated in interbacterial competition among Firmicutes. Together, this work identifies new T6SS effectors employed by a plant commensal bacterium to antagonize its competitors and broadly implicates NAD(P) ؉ -hydrolyzing enzymes as substrates of interbacterial conflict pathways found in diverse bacterial phyla.

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Vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells

Cited by 65 publications

References 40 publications

Glucose Metabolism by Escherichia coli Inhibits Vibrio cholerae Intestinal Colonization of Zebrafish

Glucose Metabolism by Escherichia coli Inhibits Vibrio cholerae Intestinal Colonization of Zebrafish

Analysis of Vibrio cholerae genomes identifies new type VI secretion system gene clusters

Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system

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