Two Independent Pathways for Self-Recognition in Proteus mirabilis Are Linked by Type VI-Dependent Export

Wenren, Larissa Man-Yin; Sullivan, Nora L.; Cardarelli, Lia; Septer, Alecia N.; Gibbs, Karine A.

doi:10.1128/mbio.00374-13

Cited by 112 publications

(190 citation statements)

References 41 publications

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“…Furthermore, MrpJ regulated genes that could be associated with virulence or immune evasion, such as lipopolysaccharide (LPS) modifications (pagP, lpxK, and msbB; Ϫ5.01-, Ϫ2.21-, and Ϫ2.94-fold, respectively). A type VI secretion system (T6SS), including effector genes idsA and PMI0750 as well as seven genes in the operon which encodes the structural proteins of the T6SS (PMI0749-0734) (60)(61)(62), was induced by MrpJ. Thus, MrpJ regulates a variety of genes that are known or hypothesized to contribute to pathogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Although T6SS is involved in virulence in a variety of pathogens (5,(73)(74)(75), its role in UTIs has not yet been investigated. Recent reports have described the role of the P. mirabilis T6SS in the competition of some strains over others (60,62), particularly when distinct isolates encounter each other while swarming. However, during in vitro swarming, the mrp operon is repressed (44).…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence. Bacterial pathogens utilize a myriad of complex regulatory networks to adapt gene expression in response to environmental cues encountered in the host. Trying to walk a fine balance of avoiding detection by the host immune system, while ensuring acquisition of all essential nutrients and promoting growth, bacteria employ transcriptional and posttranscriptional strategies to combat the host's defenses. A prominent example is the specific induction of iron and zinc uptake systems during infection, regulated by Fur and Zur, respectively, which allows pathogens to gain access to these essential transition metals in the restricted host environment (1, 2).Urinary tract infections (UTIs) are among the most common bacterial infections (3), presenting a significant public health burden amounting to annual costs of about 3.5 billion dollars in the United States alone (4). Although Proteus mirabilis causes a relatively small proportion of UTIs in healthy individuals, it is a common cause of cystitis and pyelonephritis in individuals with indwelling catheters or anatomical abnormalities of the urinary tract (4, 5).UTIs occur almost exclusively in an ascending route, meaning that bacteria of fecal origin gain entry to the bladder via the urethra and then spread to the kidneys via the ureters (4). Initially, bacteria adhere to host epithelial cells via proteinaceous supramolecular structures referred to as fimbriae (or pili) (6), which allow pathogens to withstand the mechanical flow of urine (5)...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

et al. 2015

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“…In addition, nonkin bacteria competed with each other to colonize plant roots, whereas kin strains cocolonized the same root surface. Boundary formation has been previously studied in the soil bacterium Myxococcus xantus (10) and in the pathogen P. mirabilis (16)(17)(18)20). In M. xanthus, the phenomenon was associated with competitive incompatibility of strains (10).…”

Section: Discussionmentioning

confidence: 99%

“…This Gram-negative urinary tract pathogen exhibits merging of genetically identical swarms, whereas swarms composed of different strains form a visible boundary and do not merge (16)(17)(18)(19)(20). Swarm merging has not been strictly correlated with relatedness in P. mirabilis, however, due to the lack of a diverse set of strains.…”

mentioning

confidence: 99%

Kin discrimination between sympatric Bacillus subtilis isolates

Štefanič

Kraigher

Lyons

et al. 2015

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

125

204

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Kin discrimination, broadly defined as differential treatment of conspecifics according to their relatedness, could help biological systems direct cooperative behavior toward their relatives. Here we investigated the ability of the soil bacterium Bacillus subtilis to discriminate kin from nonkin in the context of swarming, a cooperative multicellular behavior. We tested a collection of sympatric conspecifics from soil in pairwise combinations and found that despite their history of coexistence, the vast majority formed distinct boundaries when the swarms met. Some swarms did merge, and most interestingly, this behavior was only seen in the most highly related strain pairs. Overall the swarm interaction phenotype strongly correlated with phylogenetic relatedness, indicative of kin discrimination. Using a subset of strains, we examined cocolonization patterns on plant roots. Pairs of kin strains were able to cocolonize roots and formed a mixed-strain biofilm. In contrast, inoculating roots with pairs of nonkin strains resulted in biofilms consisting primarily of one strain, suggestive of an antagonistic interaction among nonkin strains. This study firmly establishes kin discrimination in a bacterial multicellular setting and suggests its potential effect on ecological interactions.swarming | biofilm | social evolution | kin recognition | antagonism

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“…Populations of genetically identical organisms merge, while populations of genetically different organisms separate and form a visible boundary (1)(2)(3)(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).…”

mentioning

confidence: 99%

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

2016

Self Cite

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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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Two Independent Pathways for Self-Recognition in Proteus mirabilis Are Linked by Type VI-Dependent Export

Cited by 112 publications

References 41 publications

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

Transcriptional Analysis of the MrpJ Network: Modulation of Diverse Virulence-Associated Genes and Direct Regulation of mrp Fimbrial and flhDC Flagellar Operons in Proteus mirabilis

Kin discrimination between sympatric Bacillus subtilis isolates

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

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