Marker for type VI secretion system effectors

Salomon, Dor; Kinch, Lisa N.; Trudgian, David C.; Guo, Xiao‐Feng; Klimko, John A.; Grishin, Nick V.; Mirzaei, Hamid; Orth, Kim

doi:10.1073/pnas.1406110111

Cited by 151 publications

(320 citation statements)

References 27 publications

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“…D has been found outside cells, and its export has been shown to be dependent on a functional T6SS (5). Consistent with these data, D contains the recently described MIX motif, which has been found among multiple T6SS effector proteins; the MIX motif is predicted to identify previously unknown substrates of the T6SS (32). In contrast, E has not been found outside cells and is predicted to be an integral inner membrane protein (5,31).…”

supporting

confidence: 62%

The Self-Identity Protein IdsD Is Communicated between Cells in Swarming Proteus mirabilis Colonies

2016

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Proteus mirabilis is a social bacterium that is capable of self (kin) versus nonself recognition. Swarming colonies of this bacterium expand outward on surfaces to centimeter-scale distances due to the collective motility of individual cells. Colonies of genetically distinct populations remain separate, while those of identical populations merge. Ids proteins are essential for this recognition behavior. Two of these proteins, IdsD and IdsE, encode identity information for each strain. These two proteins bind in vitro in an allele-restrictive manner. IdsD-IdsE binding is correlated with the merging of populations, whereas a lack of binding is correlated with the separation of populations. Key questions remained about the in vivo interactions of IdsD and IdsE, specifically, whether IdsD and IdsE bind within single cells or whether IdsD-IdsE interactions occur across neighboring cells and, if so, which of the two proteins is exchanged. Here we demonstrate that IdsD must originate from another cell to communicate identity and that this nonresident IdsD interacts with IdsE resident in the recipient cell. Furthermore, we show that unbound IdsD in recipient cells does not cause cell death and instead appears to contribute to a restriction in the expansion radius of the swarming colony. We conclude that P. mirabilis communicates IdsD between neighboring cells for nonlethal kin recognition, which suggests that the Ids proteins constitute a type of cell-cell communication. IMPORTANCEWe demonstrate that self (kin) versus nonself recognition in P. mirabilis entails the cell-cell communication of an identity-encoding protein that is exported from one cell and received by another. We further show that this intercellular exchange affects swarm colony expansion in a nonlethal manner, which adds social communication to the list of potential swarm-related regulatory factors.B acteria, such as the swarming bacterium Proteus mirabilis, can come together in groups that move rapidly across surfaces. During this swarm migration, P. mirabilis exhibits self (kin) versus nonself recognition. Populations of genetically identical organisms merge, while populations of genetically different organisms separate and form a visible boundary (1-4). The ids operon, which encodes the six proteins IdsA to IdsF, is one of the genetic loci responsible for boundary formation (2, 5, 6). Cells lacking the Ids proteins form a boundary with their wild-type parent strain (2). A functional type VI secretion system (T6SS) is essential for boundary formation (5, 7), and three Ids proteins (IdsA, IdsB, and IdsD [D]) are exported in a T6SS-dependent manner (5). T6SSs, which are widely distributed among Gram-negative bacteria, are machines that can translocate proteins (primarily lethal) from the inside of one cell directly into another cell (8-28). The action of these transferred effector proteins is inhibited through the binding of an inhibitory immunity protein in the recipient cell (15,16,18,21,22,(28)(29)(30).In addition to a functional T6SS, the Id...

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supporting

confidence: 62%

The Self-Identity Protein IdsD Is Communicated between Cells in Swarming Proteus mirabilis Colonies

2016

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“…Three of these proteins are homologs of the secreted proteobacterial T6SS structural proteins Hcp [also observed in a recent study (16)] and VgrG, and the fourth contains a PAARrepeat domain typical of T6SS adaptors (9,10). Of the two remaining proteins, BF9343_1937 lacks any known T6S effector domains, and BF9343_1928 contains a MIX domain found in other T6SS effectors (17). These proteins have no previously known function and are encoded, along with the PAAR adaptor, within cassettes A and B of B. fragilis N (Fig.…”

Section: B Fragilis Strains Encode Extensive Variation In Effector/imentioning

confidence: 74%

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Wexler

Bao

Whitney

et al. 2016

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

177

202

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The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes—one of two major phyla in the gut—also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.

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“…Especially abundant are lipase domains 34 and domains involved in binding or modification of PG, found exclusively in bacterial cell walls 35 41 , the AHH domain likely involved in killing bacteria via its putative nuclease activity 42 and DUF2235 (ref. 43), a putative hydrolase recently found to be present in T6SS effectors 44 (Table 1). Both Zeta toxin and AHH domains are found in toxin-antitoxin systems where they are inhibited by specific immunity proteins 41,42 .…”

Section: Discussionmentioning

confidence: 99%