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  1. Article ; Online: Microbial co-occurrences on catheters from long-term catheterized patients

    Taylor M. Nye / Zongsen Zou / Chloe L. P. Obernuefemann / Jerome S. Pinkner / Erin Lowry / Kent Kleinschmidt / Karla Bergeron / Aleksandra Klim / Karen W. Dodson / Ana L. Flores-Mireles / Jennifer N. Walker / Daniel Garrett Wong / Alana Desai / Michael G. Caparon / Scott J. Hultgren

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 13

    Abstract: Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in ... ...

    Abstract Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.
    Keywords Science ; Q
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia coli pyelonephritis.

    Lisa K McLellan / Michael R McAllaster / Arthur S Kim / Ľubomíra Tóthová / Patrick D Olson / Jerome S Pinkner / Allyssa L Daugherty / Teri N Hreha / James W Janetka / Daved H Fremont / Scott J Hultgren / Herbert W Virgin / David A Hunstad

    PLoS Pathogens, Vol 17, Iss 1, p e

    2021  Volume 1009314

    Abstract: Type 1 pili have long been considered the major virulence factor enabling colonization of the urinary bladder by uropathogenic Escherichia coli (UPEC). The molecular pathogenesis of pyelonephritis is less well characterized, due to previous limitations ... ...

    Abstract Type 1 pili have long been considered the major virulence factor enabling colonization of the urinary bladder by uropathogenic Escherichia coli (UPEC). The molecular pathogenesis of pyelonephritis is less well characterized, due to previous limitations in preclinical modeling of kidney infection. Here, we demonstrate in a recently developed mouse model that beyond bladder infection, type 1 pili also are critical for establishment of ascending pyelonephritis. Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H/HeN mice. We developed an in vitro model of FimH-dependent UPEC binding to renal collecting duct cells, and performed a CRISPR screen in these cells, identifying desmoglein-2 as a primary renal epithelial receptor for FimH. The mannosylated extracellular domain of human DSG2 bound directly to the lectin domain of FimH in vitro, and introduction of a mutation in the FimH mannose-binding pocket abolished binding to DSG2. In infected C3H/HeN mice, type 1-piliated UPEC and Dsg2 were co-localized within collecting ducts, and administration of mannoside FIM1033, a potent small-molecule inhibitor of FimH, significantly attenuated bacterial loads in pyelonephritis. Our results broaden the biological importance of FimH, specify the first renal FimH receptor, and indicate that FimH-targeted therapeutics will also have application in pyelonephritis.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Insights into the Microbiome of Breast Implants and Periprosthetic Tissue in Breast Implant-Associated Anaplastic Large Cell Lymphoma

    Jennifer N. Walker / Blake M. Hanson / Chloe L. Pinkner / Shelby R. Simar / Jerome S. Pinkner / Rajiv Parikh / Mark W. Clemens / Scott J. Hultgren / Terence M. Myckatyn

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract Though rare, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a CD30+ T-cell lymphoma associated with textured breast implants, has adversely impacted our perception of the safety of breast implants. Its etiology unknown, one ...

    Abstract Abstract Though rare, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a CD30+ T-cell lymphoma associated with textured breast implants, has adversely impacted our perception of the safety of breast implants. Its etiology unknown, one hypothesis suggests an initiating inflammatory stimulus, possibly infectious, triggers BIA-ALCL. We analyzed microbiota of breast, skin, implant and capsule in BIA-ALCL patients (n = 7), and controls via culturing methods, 16S rRNA microbiome sequencing, and immunohistochemistry. Alpha and beta diversity metrics and relative abundance of Gram-negative bacteria were calculated, and phylogenetic trees constructed. Staphylococcus spp., the most commonly cultured microbes, were identified in both the BIA-ALCL and contralateral control breast. The diversity of bacterial microbiota did not differ significantly between BIA-ALCL and controls for any material analyzed. Further, there were no significant differences in the relative abundance of Gram-negative bacteria between BIA-ALCL and control specimens. Heat maps suggested substantial diversity in the composition of the bacterial microbiota of the skin, breast, implant and capsule between patients with no clear trend to distinguish BIA-ALCL from controls. While we identified no consistent differences between patients with BIA-ALCL-affected and contralateral control breasts, this study provides insights into the composition of the breast microbiota in this population.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections

    Ana L. Flores-Mireles / Jennifer N. Walker / Aaron Potretzke / Henry L. Schreiber / Jerome S. Pinkner / Tyler M. Bauman / Alyssa M. Park / Alana Desai / Scott J. Hultgren / Michael G. Caparon

    mBio, Vol 7, Iss 5, p e01653-

    2016  Volume 16

    Abstract: Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. ... ...

    Abstract Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpANTD), the Ebp pilus’s adhesin. In a murine model, vaccination with EbpANTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpANTD-fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro. Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpANTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpANTD-fibrinogen interactions have considerable promise for treatment of CAUTI.
    Keywords Science ; Q ; Microbiology ; QR1-502
    Subject code 570
    Language English
    Publishing date 2016-10-01T00:00:00Z
    Publisher American Society for Microbiology
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A novel endogenous inhibitor of the secreted streptococcal NAD-glycohydrolase.

    Michael A Meehl / Jerome S Pinkner / Patricia J Anderson / Scott J Hultgren / Michael G Caparon

    PLoS Pathogens, Vol 1, Iss 4, p e

    2005  Volume 35

    Abstract: The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In ...

    Abstract The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In this report, we describe immunity factor for SPN (IFS), a novel endogenous inhibitor that is essential for SPN expression. A small protein of 161 amino acids, IFS is localized in the bacterial cytoplasmic compartment. IFS forms a stable complex with SPN at a 1:1 molar ratio and inhibits SPN's NAD-glycohydrolase activity by acting as a competitive inhibitor of its beta-NAD+ substrate. Mutational studies revealed that the gene for IFS is essential for viability in those S. pyogenes strains that express an NAD-glycohydrolase activity. However, numerous strains contain a truncated allele of ifs that is linked to an NAD-glycohydrolase-deficient variant allele of spn. Of practical concern, IFS allowed the normally toxic SPN to be produced in the heterologous host Escherichia coli to facilitate its purification. To our knowledge, IFS is the first molecularly characterized endogenous inhibitor of a bacterial beta-NAD(+)-consuming toxin and may contribute protective functions in the streptococci to afford SPN-mediated pathogenesis.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2005-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli.

    Jeffrey P Henderson / Jan R Crowley / Jerome S Pinkner / Jennifer N Walker / Pablo Tsukayama / Walter E Stamm / Thomas M Hooton / Scott J Hultgren

    PLoS Pathogens, Vol 5, Iss 2, p e

    2009  Volume 1000305

    Abstract: Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies ... ...

    Abstract Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2009-02-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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