Transcriptome of Swarming
            <i>Proteus mirabilis</i>

Pearson, Melanie M.; Rasko, David A.; Smith, Sara N.; Mobley, Harry L. T.

doi:10.1128/iai.01222-09

Cited by 90 publications

(138 citation statements)

References 67 publications

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“…In addition, swarming regulators umoA and umoB were repressed by MrpJ (Ϫ222-and Ϫ2.68-fold, respectively), while lrhA was induced (2.21-fold) (44,52,53), indicating that MrpJ not only represses motility but also interferes with swarmer cell differentiation. The cell shape-determining gene ccm, also implicated in swarming behavior (54), was the most repressed gene in the in vivo mimic strain (630-fold).…”

Section: Resultsmentioning

confidence: 93%

“…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). We speculate that the T6SS may play a swarmingindependent role during infection by mediating direct interaction with the host, perhaps mediated by secretion of a different set of effector proteins.…”

Section: Discussionmentioning

confidence: 97%

“…The P. mirabilis HI4320 microarray has been described previously (44). To measure MrpJ-regulated gene transcription, P. mirabilis HI4320, HI4320⌬mrpJ, vector control HI4320(pLX3607), or mrpJ in vivo mimic HI4320(pLX3805) were cultured to logarithmic phase with aeration (optical density at 600 nm [OD 600 ] of 0.7 to 0.9).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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: 93%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

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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“…When P. mirabilis swimmer cells differentiate into swarmer cells, flhDC transcription increases, and genes in the flagellar regulon are upregulated (16,18,19). Many regulatory and environmental factors control the expression and activity of flhDC and swarming.…”

mentioning

confidence: 99%

Loss of FliL Alters Proteus mirabilis Surface Sensing and Temperature-Dependent Swarming

Lee

Belas

2015

J Bacteriol

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Proteus mirabilis is a dimorphic motile bacterium well known for its flagellum-dependent swarming motility over surfaces. In liquid, P. mirabilis cells are 1.5-to 2.0-m swimmer cells with 4 to 6 flagella. When P. mirabilis encounters a solid surface, where flagellar rotation is limited, swimmer cells differentiate into elongated (10-to 80-m), highly flagellated swarmer cells. In order for P. mirabilis to swarm, it first needs to detect a surface. The ubiquitous but functionally enigmatic flagellar basal body protein FliL is involved in P. mirabilis surface sensing. Previous studies have suggested that FliL is essential for swarming through its involvement in viscosity-dependent monitoring of flagellar rotation. In this study, we constructed and characterized ⌬fliL mutants of P. mirabilis and Escherichia coli. Unexpectedly and unlike other fliL mutants, both P. mirabilis and E. coli ⌬fliL cells swarm (Swr ؉ ). Further analysis revealed that P. mirabilis ⌬fliL cells also exhibit an alteration in their ability to sense a surface: e.g., ⌬fliL P. mirabilis cells swarm precociously over surfaces with low viscosity that normally impede wild-type swarming. Precocious swarming is due to an increase in the number of elongated swarmer cells in the population. Loss of fliL also results in an inhibition of swarming at <30°C. E. coli ⌬fliL cells also exhibit temperature-sensitive swarming. These results suggest an involvement of FliL in the energetics and function of the flagellar motor. Most bacteria are able to live a planktonic free-living lifestyle or in a surface-attached microbial community called a "biofilm." The interchange between the motile and the sessile phases, referred to as the "swim-or-stick" switch, is not merely stochastic. Rather, the lifestyle change occurs in response to cues that a cell senses as it nears a surface (1). These surface signals are required and initiate biofilm formation (1). A fundamental question underlying the transition in lifestyle from motile to sessile phases is how does a bacterium sense a surface?Studies of many different bacterial species support the idea that surface sensing often involves the bacterial flagellum (2), which also facilitates movement toward and attachment to a surface. However, it is generally agreed that motility and biofilm formation are mutually exclusive. Moreover, flagella are used not only for swimming in liquid but also for swarming over a solid surface. Many bacterial species swarm, and often, as in Proteus mirabilis, require a surface-induced differentiated cell type, called a swarmer cell, that is elongated and hyperflagellated (3).P. mirabilis is a Gram-negative gammaproteobacterium belonging to the Enterobacteriaceae family. It is an opportunistic pathogen capable of causing urinary tract infections (UTI) (4-6). P. mirabilis is dimorphic and produces short vegetative swimmer cells (1.5 to 2.0 m in length) with a single nucleoid and 4 to 10 peritrichous flagella when cultured in nutrient broth. Conversely, when cultured on nutrient agar or in viscous en...

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“…An emphasis on pathways, networks, and systems has given rise to powerful new bioinformatics and experimental methods. Genomic, microarray, and proteomic analyses are now commonplace in IAI (25,35,40). Systems approaches can be "topdown," starting from "-omics" data and seeking to derive underlying explanatory principles, or "bottom-up," starting with molecular properties and deriving models that can subsequently be tested and validated (8).…”

mentioning

confidence: 99%