scholarly journals Evolutionary Analysis Points to Divergent Physiological Roles of Type 1 Fimbriae in Salmonella and Escherichia coli

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Dagmara I. Kisiela ◽  
Sujay Chattopadhyay ◽  
Veronika Tchesnokova ◽  
Sandip Paul ◽  
Scott J. Weissman ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Structural Diversity ◽  
Evolutionary Analysis ◽  
Content Type ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Gene Shuffling ◽  
Immune Pressure ◽  
High Level

ABSTRACTSalmonellaandEscherichia colimannose-binding type 1 fimbriae exhibit highly similar receptor specificities, morphologies, and mechanisms of assembly but are nonorthologous in nature, i.e., not closely related evolutionarily. Their operons differ in chromosomal location, gene arrangement, and regulatory components. In the current study, we performed a comparative genetic and structural analysis of the major structural subunit, FimA, fromSalmonellaandE. coliand found that FimA pilins undergo diverse evolutionary adaptation in the different species. Whereas theE. coli fimAlocus is characterized by high allelic diversity, frequent intragenic recombination, and horizontal movement,Salmonella fimAshows structural diversity that is more than 5-fold lower without strong evidence of gene shuffling or homologous recombination. In contrast toSalmonellaFimA, the amino acid substitutions in theE. colipilin heavily target the protein regions that are predicted to be exposed on the external surface of fimbriae. Altogether, our results suggest thatE. coli, but notSalmonella, type 1 fimbriae display a high level of structural diversity consistent with a strong selection for antigenic variation under immune pressure. Thus, type 1 fimbriae in these closely related bacterial species appear to function in distinctly different physiological environments.IMPORTANCEE. coliandSalmonellaare enteric bacteria that are closely related from an evolutionary perspective. They are both notorious human pathogens, though with somewhat distinct ecologies and virulence mechanisms. Type 1 fimbriae are rod-shaped surface appendages found in mostE. coliandSalmonellaisolates. In both species, they mediate bacterial adhesion to mannose receptors on host cells and share essentially the same morphology and assembly mechanisms. Here we show that despite the strong resemblances in function and structure, they are exposed to very different natural selection environments. Sequence analysis indicates thatE. coli, but notSalmonella, fimbriae are subjected to strong immune pressure, resulting in a high level of major fimbrial protein gene shuffling and interbacterial transfer. Thus, evolutionary analysis tools can provide evidence of divergent physiological roles of functionally similar traits in different bacterial species.

scholarly journals Population Variability of the FimH Type 1 Fimbrial Adhesin in Klebsiella pneumoniae

2009 ◽  
Vol 191 (6) ◽  
pp. 1941-1950 ◽  
Author(s):  
Steen G. Stahlhut ◽  
Sujay Chattopadhyay ◽  
Carsten Struve ◽  
Scott J. Weissman ◽  
Pavel Aprikian ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Point Mutations ◽  
Structural Diversity ◽  
Single Amino Acid ◽  
Adaptive Mutations ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Highly Virulent ◽  
Fimbrial Adhesin

ABSTRACT FimH is an adhesive subunit of type 1 fimbriae expressed by different enterobacterial species. The enteric bacterium Klebsiella pneumoniae is an environmental organism that is also a frequent cause of sepsis, urinary tract infection (UTI), and liver abscess. Type 1 fimbriae have been shown to be critical for the ability of K. pneumoniae to cause UTI in a murine model. We show here that the K. pneumoniae fimH gene is found in 90% of strains from various environmental and clinical sources. The fimH alleles exhibit relatively low nucleotide and structural diversity but are prone to frequent horizontal-transfer events between different bacterial clones. Addition of the fimH locus to multiple-locus sequence typing significantly improved the resolution of the clonal structure of pathogenic strains, including the K1 encapsulated liver isolates. In addition, the K. pneumoniae FimH protein is targeted by adaptive point mutations, though not to the same extent as FimH from uropathogenic Escherichia coli or TonB from the same K. pneumoniae strains. Such adaptive mutations include a single amino acid deletion from the signal peptide that might affect the length of the fimbrial rod by affecting FimH translocation into the periplasm. Another FimH mutation (S62A) occurred in the course of endemic circulation of a nosocomial uropathogenic clone of K. pneumoniae. This mutation is identical to one found in a highly virulent uropathogenic strain of E. coli, suggesting that the FimH mutations are pathoadaptive in nature. Considering the abundance of type 1 fimbriae in Enterobacteriaceae, our present finding that fimH genes are subject to adaptive microevolution substantiates the importance of type 1 fimbria-mediated adhesion in K. pneumoniae.

scholarly journals FimA, FimF, and FimH Are Necessary for Assembly of Type 1 Fimbriae on Salmonella enterica Serovar Typhimurium

2012 ◽  
Vol 80 (9) ◽  
pp. 3289-3296 ◽  
Author(s):  
Sarah A. Zeiner ◽  
Brett E. Dwyer ◽  
Steven Clegg
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Food Poisoning ◽  
Enteric Bacteria ◽  
Transcriptional Unit ◽  
Content Type ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericaserovar Typhimurium is a Gram-negative member of the familyEnterobacteriaceaeand is a common cause of bacterial food poisoning in humans. The fimbrial appendages are found on the surface of many enteric bacteria and enable the bacteria to bind to eukaryotic cells.S. Typhimurium type 1 fimbriae are characterized by mannose-sensitive hemagglutination and are assembled via the chaperone/usher pathway.S. Typhimurium type 1 fimbrial proteins are encoded by thefimgene cluster (fimAICDHFZYW), withfimAICDHFexpressed as a single transcriptional unit. The structural components of the fimbriae are FimA (major subunit), FimI, FimH (adhesin), and FimF (adaptor). In order to determine which components are required for fimbrial formation inS. Typhimurium, mutations infimA,fimI,fimH, andfimFwere constructed and examined for their ability to produce surface-assembled fimbriae.S. Typhimurium SL1344ΔfimA, -ΔfimH, and -ΔfimFmutants were unable to assemble fimbriae, indicating that these genes are necessary for fimbrial production inS. Typhimurium. However, SL1344ΔfimIwas able to assemble fimbriae. InEscherichia colitype 1 and Pap fimbriae, at least two adaptors are expressed in addition to the adhesins. However,E. colitype 1 and Pap fimbriae have been reported to be able to assemble fimbriae in the absence of these proteins. These results suggest differences between theS. Typhimurium type 1 fimbrial system and theE. colitype 1 and Pap fimbrial systems.

scholarly journals High-Resolution Two-Locus Clonal Typing of Extraintestinal Pathogenic Escherichia coli

2012 ◽  
Vol 78 (5) ◽  
pp. 1353-1360 ◽  
Author(s):  
Scott J. Weissman ◽  
James R. Johnson ◽  
Veronika Tchesnokova ◽  
Mariya Billig ◽  
Daniel Dykhuizen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Species ◽  
Discrimination Power ◽  
Content Type ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Sequence Types ◽  
Fimbrial Adhesin ◽  
Internal Fragment

ABSTRACTMultilocus sequence typing (MLST) is usually based on the sequencing of 5 to 8 housekeeping loci in the bacterial chromosome and has provided detailed descriptions of the population structure of bacterial species important to human health. However, even strains with identical MLST profiles (known as sequence types or STs) may possess distinct genotypes, which enable different eco- or pathotypic lifestyles. Here we describe a two-locus, sequence-based typing scheme forEscherichia colithat utilizes a 489-nucleotide (nt) internal fragment offimH(encoding the type 1 fimbrial adhesin) and the 469-nt internalfumCfragment used in standard MLST. Based on sequence typing of 191 model commensal and pathogenic isolates plus 853 freshly isolated clinicalE. colistrains, this 2-locus approach—which we call CH (fumC/fimH) typing—consistently yielded more haplotypes than standard 7-locus MLST, splitting large STs into multiple clonal subgroups and often distinguishing different within-ST eco- and pathotypes. Furthermore, specific CH profiles corresponded to specific STs, or ST complexes, with 95% accuracy, allowing excellent prediction of MLST-based profiles. Thus, 2-locus CH typing provides a genotyping tool for molecular epidemiology analysis that is more economical than standard 7-locus MLST but has superior clonal discrimination power and, at the same time, corresponds closely to MLST-based clonal groupings.

scholarly journals Enhancing Terpene Yield from Sugars via Novel Routes to 1-Deoxy-d-Xylulose 5-Phosphate

2014 ◽  
Vol 81 (1) ◽  
pp. 130-138 ◽  
Author(s):  
James Kirby ◽  
Minobu Nishimoto ◽  
Ruthie W. N. Chow ◽  
Edward E. K. Baidoo ◽  
George Wang ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Xylose Reductase ◽  
Pentose Phosphate ◽  
Terpene Biosynthesis ◽  
Content Type ◽  
E Coli ◽  
Pathway Expression ◽  
Terpene Synthesis ◽  
Selection For

ABSTRACTTerpene synthesis in the majority of bacterial species, together with plant plastids, takes place via the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway. The first step of this pathway involves the condensation of pyruvate and glyceraldehyde 3-phosphate by DXP synthase (Dxs), with one-sixth of the carbon lost as CO2. A hypothetical novel route from a pentose phosphate to DXP (nDXP) could enable a more direct pathway from C5sugars to terpenes and also circumvent regulatory mechanisms that control Dxs, but there is no enzyme known that can convert a sugar into its 1-deoxy equivalent. Employing a selection for complementation of adxsdeletion inEscherichia coligrown on xylose as the sole carbon source, we uncovered two candidate nDXP genes. Complementation was achieved either via overexpression of the wild-typeE. coliyajOgene, annotated as a putative xylose reductase, or via various mutations in the nativeribBgene.In vitroanalysis performed with purified YajO and mutant RibB proteins revealed that DXP was synthesized in both cases from ribulose 5-phosphate (Ru5P). We demonstrate the utility of these genes for microbial terpene biosynthesis by engineering the DXP pathway inE. colifor production of the sesquiterpene bisabolene, a candidate biodiesel. To further improve flux into the pathway from Ru5P, nDXP enzymes were expressed as fusions to DXP reductase (Dxr), the second enzyme in the DXP pathway. Expression of a Dxr-RibB(G108S) fusion improved bisabolene titers more than 4-fold and alleviated accumulation of intracellular DXP.

scholarly journals Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli.

1996 ◽  
Vol 183 (3) ◽  
pp. 1037-1044 ◽  
Author(s):  
M Hedlund ◽  
M Svensson ◽  
A Nilsson ◽  
R D Duan ◽  
C Svanborg
Keyword(s):  
Escherichia Coli ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Human Kidney ◽  
Cytokine Response ◽  
Protein Kinase Inhibitors ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Outer Leaflet

Escherichia coli express fimbriae-associated adhesins through which they attach to mucosal cells and activate a cytokine response. The receptors for E. coli P fimbriae are the globoseries of glycosphingolipids; Gal alpha 1-->4Gal beta-containing oligosaccharides bound to ceramide in the outer leaflet of the lipid bilayer. The receptors for type 1 fimbriae are mannosylated glycoproteins rather than glycolipids. This study tested the hypothesis that P-fimbriated E. coli elicit a cytokine response through the release of ceramide in the receptor-bearing cell. We used the A498 human kidney cell line, which expressed functional receptors for P and type 1 fimbriae and secreted higher levels of interleukin (IL)-6 when exposed to the fimbriated strains than to isogenic nonfimbriated controls. P-fimbriated E. coli caused the release of ceramide and increased the phosphorylation of ceramide to ceramide 1-phosphate. The IL-6 response to P-fimbriated E. coli was reduced by inhibitors of serine/threonine kinases but not by other protein kinase inhibitors. In contrast, ceramide levels were not influenced by type 1-fimbriated E. coli, and the IL-6 response was insensitive to the serine/threonine kinase inhibitors. These results demonstrate that the ceramide-signaling pathway is activated by P-fimbriated E. coli, and that the receptor specificity of the P fimbriae influences this process. We propose that this activation pathway contributes to the cytokine induction by P-fimbriated E. coli in epithelial cells.

scholarly journals A New Clone Sweeps Clean: the Enigmatic Emergence of Escherichia coli Sequence Type 131

2014 ◽  
Vol 58 (9) ◽  
pp. 4997-5004 ◽  
Author(s):  
Ritu Banerjee ◽  
James R. Johnson
Keyword(s):  
Escherichia Coli ◽  
Sequence Type ◽  
Rapid Expansion ◽  
Future Research ◽  
Content Type ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Phylogenetic Studies ◽  
Ecological Success

ABSTRACTEscherichia colisequence type 131 (ST131) is an extensively antimicrobial-resistantE. coliclonal group that has spread explosively throughout the world. Recent molecular epidemiologic and whole-genome phylogenetic studies have elucidated the fine clonal structure of ST131, which comprises multiple ST131 subclones with distinctive resistance profiles, including the (nested) H30, H30-R, and H30-Rx subclones. The most prevalent ST131 subclone, H30, arose from a single common fluoroquinolone (FQ)-susceptible ancestor containing allele 30 offimH(type 1 fimbrial adhesin gene). An early H30 subclone member acquired FQ resistance and launched the rapid expansion of the resulting FQ-resistant subclone, H30-R. Subsequently, a member of H30-R acquired the CTX-M-15 extended-spectrum beta-lactamase and launched the rapid expansion of the CTX-M-15-containing subclone within H30-R, H30-Rx. Clonal expansion clearly is now the dominant mechanism for the rising prevalence of both FQ resistance and CTX-M-15 production in ST131 and inE. coligenerally. Reasons for the successful dissemination and expansion of the key ST131 subclones remain undefined but may include increased transmissibility, greater ability to colonize and/or persist in the intestine or urinary tract, enhanced virulence, and more-extensive antimicrobial resistance compared to otherE. coli. Here we discuss the epidemiology and molecular phylogeny of ST131 and its key subclones, possible mechanisms for their ecological success, implications of their widespread dissemination, and future research needs.

scholarly journals Combined Action of Human Commensal Bacteria and Amorphous Silica Nanoparticles on the Viability and Immune Responses of Dendritic Cells

2017 ◽  
Vol 24 (10) ◽  
Author(s):  
Giulia Malachin ◽  
Elisa Lubian ◽  
Fabrizio Mancin ◽  
Emanuele Papini ◽  
Regina Tavano
Keyword(s):  
Dendritic Cells ◽  
Silica Nanoparticles ◽  
Amorphous Silica ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Commensal Bacteria ◽  
Content Type ◽  
E Coli ◽  
Synergistic Induction ◽  
Ifn Γ

ABSTRACT Dendritic cells (DCs) regulate the host-microbe balance in the gut and skin, tissues likely exposed to nanoparticles (NPs) present in drugs, food, and cosmetics. We analyzed the viability and the activation of DCs incubated with extracellular media (EMs) obtained from cultures of commensal bacteria (Escherichia coli, Staphylococcus epidermidis) or pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) in the presence of amorphous silica nanoparticles (SiO2 NPs). EMs and NPs synergistically increased the levels of cytotoxicity and cytokine production, with different nanoparticle dose-response characteristics being found, depending on the bacterial species. E. coli and S. epidermidis EMs plus NPs at nontoxic doses stimulated the secretion of interleukin-1β (IL-1β), IL-12, IL-10, and IL-6, while E. coli and S. epidermidis EMs plus NPs at toxic doses stimulated the secretion of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, and IL-5. On the contrary, S. aureus and P. aeruginosa EMs induced cytokines only when they were combined with NPs at toxic concentrations. The induction of maturation markers (CD86, CD80, CD83, intercellular adhesion molecule 1, and major histocompatibility complex class II) by commensal bacteria but not by pathogenic ones was improved in the presence of noncytotoxic SiO2 NP doses. DCs consistently supported the proliferation and differentiation of CD4+ and CD8+ T cells secreting IFN-γ and IL-17A. The synergistic induction of CD86 was due to nonprotein molecules present in the EMs from all bacteria tested. At variance with this finding, the synergistic induction of IL-1β was prevalently mediated by proteins in the case of E. coli EMs and by nonproteins in the case of S. epidermidis EMs. A bacterial costimulus did not act on DCs after adsorption on SiO2 NPs but rather acted as an independent agonist. The inflammatory and immune actions of DCs stimulated by commensal bacterial agonists might be altered by the simultaneous exposure to engineered or environmental NPs.

scholarly journals Spatiotemporal Distribution of Pseudomonas aeruginosa Alkyl Quinolones under Metabolic and Competitive Stress

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Tianyuan Cao ◽  
Jonathan V. Sweedler ◽  
Paul W. Bohn ◽  
Joshua D. Shrout
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Species ◽  
Metabolic Stress ◽  
Opportunistic Pathogen ◽  
Cell Interaction ◽  
Chemical Imaging ◽  
Carbon Limitation ◽  
Bacterial Strains ◽  
Content Type ◽  
High Level

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen important to diseases such as cystic fibrosis. P. aeruginosa has multiple quorum-sensing (QS) systems, one of which utilizes the signaling molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). Here, we use hyperspectral Raman imaging to elucidate the spatiotemporal PQS distributions that determine how P. aeruginosa regulates surface colonization and its response to both metabolic stress and competition from other bacterial strains. These chemical imaging experiments illustrate the strong link between environmental challenges, such as metabolic stress caused by nutritional limitations or the presence of another bacterial species, and PQS signaling. Metabolic stress elicits a complex response in which limited nutrients induce the bacteria to produce PQS earlier, but the bacteria may also pause PQS production entirely if the nutrient concentration is too low. Separately, coculturing P. aeruginosa in the proximity of another bacterial species, or its culture supernatant, results in earlier production of PQS. However, these differences in PQS appearance are not observed for all alkyl quinolones (AQs) measured; the spatiotemporal response of 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) is highly uniform for most conditions. These insights on the spatiotemporal distributions of quinolones provide additional perspective on the behavior of P. aeruginosa in response to different environmental cues. IMPORTANCE Alkyl quinolones (AQs), including Pseudomonas quinolone signal (PQS), made by the opportunistic pathogen Pseudomonas aeruginosa have been associated with both population density and stress. The regulation of AQ production is known to be complex, and the stimuli that modulate AQ responses are not fully clear. Here, we have used hyperspectral Raman chemical imaging to examine the temporal and spatial profiles of AQs exhibited by P. aeruginosa under several potentially stressful conditions. We found that metabolic stress, effected by carbon limitation, or competition stress, effected by proximity to other species, resulted in accelerated PQS production. This competition effect did not require cell-to-cell interaction, as evidenced by the fact that the addition of supernatants from either Escherichia coli or Staphylococcus aureus led to early appearance of PQS. Lastly, the fact that these modulations were observed for PQS but not for all AQs suggests a high level of complexity in AQ regulation that remains to be discerned.

scholarly journals Escherichia coli Clonobiome: Assessing the Strain Diversity in Feces and Urine by Deep Amplicon Sequencing

2019 ◽  
Vol 85 (23) ◽  
Author(s):  
Sofiya G. Shevchenko ◽  
Matthew Radey ◽  
Veronika Tchesnokova ◽  
Dagmara Kisiela ◽  
Evgeni V. Sokurenko
Keyword(s):  
Bacterial Species ◽  
Clonal Diversity ◽  
Amplicon Sequencing ◽  
Multidrug Resistant ◽  
Full Understanding ◽  
Highly Pathogenic ◽  
Content Type ◽  
E Coli ◽  
Strain Diversity ◽  
Healthy Carriers

ABSTRACT While microbiome studies have focused on diversity at the species level or higher, bacterial species in microbiomes are represented by different, often multiple, strains. These strains could be clonally and phenotypically very different, making assessment of strain content vital to a full understanding of microbiome function. This is especially important with respect to antibiotic-resistant strains, the clonal spread of which may be dependent on competition between them and susceptible strains from the same species. The pandemic, multidrug-resistant, and highly pathogenic Escherichia coli subclone ST131-H30 (H30) is of special interest, as it has already been found persisting in the gut and bladder in healthy people. In order to rapidly assess E. coli clonal diversity, we developed a novel method based on deep sequencing of two loci used for sequence typing, along with an algorithm for analysis of the resulting data. Using this method, we assessed fecal and urinary samples from healthy women carrying H30 and were able to uncover considerable diversity, including strains with frequencies at <1% of the E. coli population. We also found that, even in the absence of antibiotic use, H30 could completely dominate the gut and, especially, urine of healthy carriers. Our study offers a novel tool for assessing a species’ clonal diversity (clonobiome) within the microbiome, which could be useful in studying the population structure and dynamics of multidrug-resistant and/or highly pathogenic strains in their natural environments. IMPORTANCE Bacterial species in the microbiome are often represented by multiple genetically and phenotypically different strains, making insight into subspecies diversity critical to a full understanding of the microbiome, especially with respect to opportunistic pathogens. However, methods allowing efficient high-throughput clonal typing are not currently available. This study combines a conventional E. coli typing method with deep amplicon sequencing to allow analysis of many samples concurrently. While our method was developed for E. coli, it may be adapted for other species, allowing microbiome researchers to assess clonal strain diversity in natural samples. Since assessment of subspecies diversity is particularly important for understanding the spread of antibiotic resistance, we applied our method to the study of a pandemic multidrug-resistant E. coli clone. The results we present suggest that this clone could be highly competitive in healthy carriers and that the mechanisms of colonization by such clones need to be studied.

scholarly journals Altered Regulation of the Diguanylate Cyclase YaiC Reduces Production of Type 1 Fimbriae in a Pst Mutant of Uropathogenic Escherichia coli CFT073

2017 ◽  
Vol 199 (24) ◽  
Author(s):  
Sébastien Crépin ◽  
Gaëlle Porcheron ◽  
Sébastien Houle ◽  
Josée Harel ◽  
Charles M. Dozois
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Molecular Mechanisms ◽  
Diguanylate Cyclase ◽  
Altered Expression ◽  
Content Type ◽  
Type 1 Fimbriae ◽  
Tract Infections ◽  
Pst System

ABSTRACT The pst gene cluster encodes the phosphate-specific transport (Pst) system. Inactivation of the Pst system constitutively activates the two-component regulatory system PhoBR and attenuates the virulence of pathogenic bacteria. In uropathogenic Escherichia coli strain CFT073, attenuation by inactivation of pst is predominantly attributed to the decreased expression of type 1 fimbriae. However, the molecular mechanisms connecting the Pst system and type 1 fimbriae are unknown. To address this, a transposon library was constructed in the pst mutant, and clones were tested for a regain in type 1 fimbrial production. Among them, the diguanylate cyclase encoded by yaiC (adrA in Salmonella) was identified to connect the Pst system and type 1 fimbrial expression. In the pst mutant, the decreased expression of type 1 fimbriae is connected by the induction of yaiC. This is predominantly due to altered expression of the FimBE-like recombinase genes ipuA and ipbA, affecting at the same time the inversion of the fim promoter switch (fimS). In the pst mutant, inactivation of yaiC restored fim-dependent adhesion to bladder cells and virulence. Interestingly, the expression of yaiC was activated by PhoB, since transcription of yaiC was linked to the PhoB-dependent phoA-psiF operon. As YaiC is involved in cyclic di-GMP (c-di-GMP) biosynthesis, an increased accumulation of c-di-GMP was observed in the pst mutant. Hence, the results suggest that one mechanism by which deletion of the Pst system reduces the expression of type 1 fimbriae is through PhoBR-mediated activation of yaiC, which in turn increases the accumulation of c-di-GMP, represses the fim operon, and, consequently, attenuates virulence in the mouse urinary tract infection model. IMPORTANCE Urinary tract infections (UTIs) are common bacterial infections in humans. They are mainly caused by uropathogenic Escherichia coli (UPEC). We previously showed that interference with phosphate homeostasis decreases the expression of type 1 fimbriae and attenuates UPEC virulence. Herein, we identified that alteration of the phosphate metabolism increases production of the signaling molecule c-di-GMP, which in turn decreases the expression of type 1 fimbriae. We also determine the regulatory cascade leading to the accumulation of c-di-GMP and identify the Pho regulon as new players in c-di-GMP-mediated cell signaling. By understanding the molecular mechanisms leading to the expression of virulence factors, we will be in a better position to develop new therapeutics.

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