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PROVIDER: PRJNA1145476 | ENA |
REPOSITORIES: ENA
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Project description:This series of microarrays compares gene expression by the bacterial pathogen Proteus mirabilis when the transcriptional regulator mrpJ is deleted or induced to levels found during experimental urinary tract infection. The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections. Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for successful 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 a wide array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking expression levels that occur during UTI leads to differential expression of 217 genes related to, among others, bacterial virulence, type VI secretion and metabolism. We probed the molecular mechanism of transcriptional regulation through MrpJ using reporter assays and chromatin immunoprecipitation (ChIP). Two virulence-associated target genes, the flagellar master regulator flhDC and mrp itself, appear to be regulated through a binding site proximal to the transcriptional start, complemented by a more distantly situated enhancer site. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observe that mrpJ is widely conserved in a collection of recent clinical isolates, leading us to conclude that our results elucidate an unanticipated role of MrpJ as a global regulator of P. mirabilis virulence. Four biological replicates were analyzed for each set of arrays (P. mirabilis HI4320 wild type vs. ΔmrpJ, and vector pLX3607 vs. mrpJ plasmid pLX3805).
2015-04-13 | E-GEOD-63321 | biostudies-arrayexpress
Project description:The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen Candida albicans adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast Candida albicans and the Gram-negative bacterium Proteus mirabilis resulting in enhanced host cell damage. This synergistic effect was conserved across different P. mirabilis isolates and occurred also with non-albicans Candida species and C. albicans mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the P. mirabilis hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between Candida and Proteus is induced by contact, but also by soluble factors. Specifically, we identified Candida-mediated glucose consumption and farnesol production as potential triggers for Proteus virulence. In summary, our study demonstrates that coinfection of enterocytes with C. albicans and P. mirabilis can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification via nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination.
2022-05-09 | PXD031222 | Pride
Project description:This series of microarrays compares gene expression by the bacterial pathogen Proteus mirabilis when the transcriptional regulator mrpJ is deleted or induced to levels found during experimental urinary tract infection. The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections. Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for successful 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 a wide array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking expression levels that occur during UTI leads to differential expression of 217 genes related to, among others, bacterial virulence, type VI secretion and metabolism. We probed the molecular mechanism of transcriptional regulation through MrpJ using reporter assays and chromatin immunoprecipitation (ChIP). Two virulence-associated target genes, the flagellar master regulator flhDC and mrp itself, appear to be regulated through a binding site proximal to the transcriptional start, complemented by a more distantly situated enhancer site. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observe that mrpJ is widely conserved in a collection of recent clinical isolates, leading us to conclude that our results elucidate an unanticipated role of MrpJ as a global regulator of P. mirabilis virulence.
2015-04-13 | GSE63321 | GEO
Project description:Individual cells of the bacterium Proteus mirabilis can elongate up to 40- fold on surfaces before engaging in a cooperative surface-based motility termed swarming. How cells regulate this dramatic morphological remodeling remains an open question. In this paper, we move forward the understanding of this regulation by demonstrating that P. mirabilis requires the gene rffG for swarmer cell elongation and subsequent swarm motility.
2018-07-04 | GSE116587 | GEO
Project description:Many clinically relevant bacterial pathogens are encapsulated, as exemplified by Salmonella enterica serovar Typhi. S. Typhi, the causative agent of the life-threatening systemic disease enteric fever, expresses Vi as the outermost surface glycan that protects the bacteria from host immune responses. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi strains, as well as Vi variants, are widespread globally. Our WGS analyses indicate that almost all S. Typhi clinical isolates are susceptible to rifamycins and azithromycin. Rifampin, even at sub-MIC levels, eliminates the protective capsule Vi, a process referred to as ‘decapsulation’, thereby enhancing bacterial clearance. Antibiotic-mediated decapsulation of S. Typhi appears specific to rifamycins, since azithromycin does not decapsulate S. Typhi. Rifampin mediated decapsulation occurs at the transcriptional level, where both high AT content and specific RpoB residues play a crucial role. Rifampin also effectively decapsulates Vi variants, which accounts for 1 in 5 S. Typhi isolates at the global level. A mechanistic explanation for rifampin mediated decapsulation of S. Typhi appears to be applicable to other encapsulated pathogens, including S. Paratyphi C.
2025-05-15 | GSE295448 | GEO
Project description:Proteus mirabilis is a leading cause of catheter-associated urinary tract infections (UTIs) and urolithiasis. The transcriptional regulator MrpJ inversely modulates two critical aspects of P. mirabilis UTI progression: fimbria-mediated attachment to the urinary tract, and flagella-mediated motility. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) was used for the first time in a CAUTI pathogen to probe for in vivo direct targets of MrpJ. ChIP-seq revealed 81 78 direct MrpJ targets, including genes for motility, fimbriae and a type VI secretion system (T6SS), and the putative MrpJ binding sequence ACnCnnnnnnnGnGT.
2018-08-10 | GSE96042 | GEO
Project description:The enteric bacterium Proteus mirabilis is a common cause of complicated urinary tract infections. In the study, microrarrays were used to analyze P. mirabilis gene expression in vivo from experimentally infected mice. Urine was collected at 1, 3, and 7d postinfection, and RNA was isolated from bacteria in the urine for transcriptional analysis. Across 9 microarrays, 471 genes were upregulated and 82 were downregulated in vivo compared to in vitro broth culture. Genes upregulated in vivo encoded MR/P fimbriae, urease, iron uptake systems, amino acid and peptide transporters, pyruvate metabolism, and portions of the TCA cycle. Flagella were downregulated. Ammonia assimilation gene glnA (glutamine synthetase) was repressed in vivo while gdhA (glutamate dehydrogenase) was upregulated in vivo. Contrary to our expectations, ammonia availability due to urease activity in P. mirabilis did not drive this gene expression. A gdhA mutant was growth-deficient in minimal medium with citrate as the sole carbon source, and loss of gdhA resulted in a significant fitness defect in the mouse model of urinary tract infection. Unlike Escherichia coli, which represses gdhA and upregulates glnA in vivo and cannot utilize citrate, the data suggest that P. mirabilis uses glutamate dehydrogenase to monitor carbon-nitrogen balance, and this ability contributes to the pathogenic potential of P. mirabilis in the urinary tract. Voided urine from female CBA/J mice infected with Proteus mirabilis was collected and pooled in RNA stabilizing reagent (RNAprotect). Urine was collected at 1, 3, and 7 d postinfection. RNA was isolated from urine and log-phase LB cultures, converted to cDNA, and labeled with CyDye. Three arrays were completed per time point (9 arrays total). Slides were scanned with a ScanArray Express microarray scanner (Perkin Elmer) at 10 μm resolution and quantified using ScanArray Express software. Resulting data were normalized by total intensity and median spot intensities were identified using MIDAS (v. 2.22) software.
2011-11-29 | E-GEOD-25977 | biostudies-arrayexpress
Project description:WGS of multidrug resistant Pseudomonas aeruginosa clinical isolates from neonatal intensive care unit
| PRJNA863458 | ENA