Genetic Analysis of the Role of
            <i>yfiR</i>
            in the Ability of Escherichia coli CFT073 To Control Cellular Cyclic Dimeric GMP Levels and To Persist in the Urinary Tract

Raterman, Erica L.; Shapiro, Daniel D.; Stevens, Daniel J.; Schwartz, Kevin J.; Welch, Rodney A.

doi:10.1128/iai.01396-12

Cited by 34 publications

(41 citation statements)

References 56 publications

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“…Additionally, ⌬yfiR strains were attenuated in their swimming motility (see Fig. S3B in the supplemental material), similar to results seen with E. coli CFT073 (52).…”

Section: Yfin and Yfir Can Control Cellulose Production In Uti89supporting

confidence: 75%

“…YfiN homodimerization is inhibited by the periplasmic protein YfiR (53,54). yfiRNB are in a single operon in E. coli, and YfiR and YfiN have similar activities in E. coli as those in P. aeruginosa (51)(52)(53)59). Previous work has also shown that the YfiN homolog AwsR controls Pseudomonas fluorescens cellulose and biofilm formation (60), and in Yersinia pestis, the YfiN and YfiR homologs, HmsD and HmsC, respectively, contribute to biofilm formation and the blockage of blood intake in the rat flea Xenopsylla cheopis (61,62).…”

Section: Discussionmentioning

confidence: 99%

“…In Y. pestis, biofilm formation was only modestly affected by deletion or overexpression of the YfiB homolog HmsE (61,62). In UPEC strain CFT073, yfiR deletion leads to an increase in cellulose and curli production along with attenuation of bladder and kidney titers in a murine urinary tract infection (UTI) model (52). In UTI89, a yfiLR::Tn mutant has decreased bladder titers, intracellular bacterial communities, and motility (57).…”

Section: Discussionmentioning

confidence: 99%

“…YfiN is a diguanylate cyclase encoded within the yfiRNB operon that, when activated, contributes to biofilm formation via the production of c-di-GMP (52,53). A clean deletion of yfiN was constructed in the UTI89 ⌬csgD ⌬dsbB background.…”

Section: Yfin and Yfir Can Control Cellulose Production In Uti89mentioning

confidence: 99%

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The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli

2014

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The bacterial extracellular matrix encases cells and protects them from host-related and environmental insults. The Escherichia coli master biofilm regulator CsgD is required for the production of the matrix components curli and cellulose. CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose production through cyclic di-GMP (c-di-GMP). Here, we identified and characterized a CsgD-and AdrA-independent cellulose production pathway that was maximally active when cultures were grown under reducing conditions or when the disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose activation pathway was dependent on a second diguanylate cyclase, called YfiN. c-di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and deletion of yfiR promoted CsgD-independent cellulose production. Conversely, when YfiR was overexpressed, cellulose production was decreased. Finally, we found that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions and mutations in the DSB system caused hyperactivation of YfiN and subsequent CsgD-independent cellulose production.

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“…Additionally, ⌬yfiR strains were attenuated in their swimming motility (see Fig. S3B in the supplemental material), similar to results seen with E. coli CFT073 (52).…”

Section: Yfin and Yfir Can Control Cellulose Production In Uti89supporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Yfin and Yfir Can Control Cellulose Production In Uti89mentioning

confidence: 99%

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The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli

2014

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“…The mrkJ gene (located immediately upstream of mrkHI) encodes a phosphodiesterase enzyme that degrades intracellular c-di-GMP (8,26), while the yfiN gene (located in the yfiRNB operon) encodes a diguanylate cyclase that synthesizes c-di-GMP (8,34). To investigate whether changes in the concentration of intracellular c-di-GMP affect mrkH expression, we compared the levels of MrkH-mediated mrkH gene expression in ⌬mrkJ and ⌬yfiRNB K. pneumoniae mutants and their complemented plasmid strains by performing a real-time quantitative PCR assay.…”

Section: Expression Of Mrkhi Is Influenced By Mrkj-and Yfin-mediated mentioning

confidence: 99%

Positive Autoregulation ofmrkHIby the Cyclic Di-GMP-Dependent MrkH Protein in the Biofilm Regulatory Circuit of Klebsiella pneumoniae

Tan¹,

Wilksch²,

Hocking³

et al. 2015

J. Bacteriol.

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Klebsiella pneumoniae is an important cause of nosocomial infections, primarily through the formation of surface-associated biofilms to promote microbial colonization on host tissues. Expression of type 3 fimbriae by K. pneumoniae facilitates surface adherence, a process strongly activated by the cyclic di-GMP (c-di-GMP)-dependent transcriptional activator MrkH. In this study, we demonstrated the critical importance of MrkH in facilitating K. pneumoniae attachment on a variety of medically relevant materials and demonstrated the mechanism by which bacteria activate expression of type 3 fimbriae to colonize these materials. Sequence analysis revealed a putative MrkH recognition DNA sequence ("MrkH box"; TATCAA) located in the regulatory region of the mrkHI operon. Mutational analysis, electrophoretic mobility shift assay, and quantitative PCR experiments demonstrated that MrkH binds to the cognate DNA sequence to autoregulate mrkHI expression in a c-di-GMP-dependent manner. A half-turn deletion, but not a full-turn deletion, between the MrkH box and the ؊35 promoter element rendered MrkH ineffective in activating mrkHI expression, implying that a direct interaction between MrkH and RNA polymerase exists. In vivo analyses showed that residues L260, R265, N268, C269, E273, and I275 in the C-terminal domain of the RNA polymerase ␣ subunit are involved in the positive control of mrkHI expression by MrkH and revealed the regions of MrkH required for DNA binding and transcriptional activation. Taken together, the data suggest a model whereby c-di-GMP-dependent MrkH recruits RNA polymerase to the mrkHI promoter to autoactivate mrkH expression. Increased MrkH production subsequently drives mrkABCDF expression when activated by c-di-GMP, leading to biosynthesis of type 3 fimbriae and biofilm formation. IMPORTANCEBacterial biofilms can cause persistent infections that are refractory to antimicrobial treatments. This study investigated how a commonly encountered hospital-acquired pathogen, Klebsiella pneumoniae, controls the expression of MrkH, the principal regulator of type 3 fimbriae and biofilm formation. We discovered a regulatory circuit whereby MrkH acts as a c-di-GMP-dependent transcriptional activator of both the gene cluster of type 3 fimbriae and the mrkHI operon. In this positive-feedback loop, whereby MrkH activates its own production, K. pneumoniae has evolved a mechanism to ensure rapid MrkH production, expression of type 3 fimbriae, and subsequent biofilm formation under favorable conditions. Deciphering the molecular mechanisms of biofilm formation by bacterial pathogens is important for the development of innovative treatment strategies for biofilm infections. Biofilm-related infections substantially contribute to patient morbidity and place a significant burden on health care systems. The evolution of high-technology medicine such as intensive and invasive hospital care practices and immunosuppressive therapy and the emergence of multiply antibiotic-resistant organisms have contributed to the rise...

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Cyclic‐di‐GMP regulation of virulence in bacterial pathogens

Hall

Lee

2017

WIREs RNA

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Signaling pathways allow bacteria to adapt to changing environments. For pathogenic bacteria, signaling pathways allow for timely expression of virulence factors and the repression of antivirulence factors within the mammalian host. As the bacteria exit the mammalian host, signaling pathways enable the expression of factors promoting survival in the environment and/or nonmammalian hosts. One such signaling pathway uses the dinucleotide cyclic-di-GMP (c-di-GMP), and many bacterial genomes encode numerous proteins that are responsible for synthesizing and degrading c-di-GMP. Once made, c-di-GMP binds to individual protein and RNA receptors to allosterically alter the macromolecule function to drive phenotypic changes. Each bacterial genome encodes unique sets of genes for c-di-GMP signaling and virulence factors so the regulation by c-di-GMP is organism specific. Recent works have pointed to evidence that c-di-GMP regulates virulence in different bacterial pathogens of mammalian hosts. In this review, we discuss the criteria for determining the contribution of signaling nucleotides to pathogenesis using a well-characterized signaling nucleotide, cyclic AMP (cAMP), in Pseudomonas aeruginosa. Using these criteria, we review the roles of c-di-GMP in mediating virulence and highlight common themes that exist among eight diverse pathogens that cause different diseases through different routes of infection and transmission. © 2017 Wiley Periodicals, Inc. How to cite this article:WIREs RNA 2018, 9:e1454. doi: 10.1002/wrna.1454 INTRODUCTIONB is-(3 0 -5 0 )-cyclic dimeric guanosine monophosphate (c-di-GMP) is a widely utilized signaling pathway that regulates bacterial adaptation to different environments. 1 C-di-GMP is synthesized from two GTP by diguanylate cyclases (DGCs) that contain a GGDEF domain and degraded into pGpG by phosphodiesterases (PDE-As) that contain EAL or HD-GYP domain. Signaling by c-di-GMP is completed when pGpG is degraded further to GMP by oligoribonuclease and related RNA degradation enzymes. [2][3][4] Thus, c-di-GMP represents one of the shortest signaling ribonucleotides. In addition, a number of genes can encode proteins with both GGDEF and EAL domains (GGDEF-EAL), indicating that levels of c-di-GMP in the cell are regulated by a complicated number of synthetic and degradative enzymes. Once made, c-di-GMP binds a diverse set of protein receptors and RNA riboswitches. 1 C-di-GMP binding to molecular receptors allosterically alters their function and downstream cellular phenotypes. 5 Genes encoding c-di-GMP signaling components are found in a large number of bacterial pathogens. This review seeks to cover the contribution of c-di-GMP signaling to bacterial pathogenesis for a number of different pathogens to identify common themes. For this review, virulence and pathogenesis is considered as the ability of the bacteria to replicate and cause disease symptoms in the mammalian host. Owing to space limitation, for each pathogen, we have referenced reviews that cover their virulence factors and their c...

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Genetic Analysis of the Role of yfiR in the Ability of Escherichia coli CFT073 To Control Cellular Cyclic Dimeric GMP Levels and To Persist in the Urinary Tract

Cited by 34 publications

References 56 publications

The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli

The Disulfide Bonding System Suppresses CsgD-Independent Cellulose Production in Escherichia coli

Positive Autoregulation ofmrkHIby the Cyclic Di-GMP-Dependent MrkH Protein in the Biofilm Regulatory Circuit of Klebsiella pneumoniae

Cyclic‐di‐GMP regulation of virulence in bacterial pathogens

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