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  1. Article ; Online: Establishing the role of the gut microbiota in susceptibility to recurrent urinary tract infections

    Colin J. Worby / Benjamin S. Olson / Karen W. Dodson / Ashlee M. Earl / Scott J. Hultgren

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 5

    Keywords Medicine ; R
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. 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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  3. Article ; Online: Adhesive Pili in UTI Pathogenesis and Drug Development

    Caitlin N. Spaulding / Scott J. Hultgren

    Pathogens, Vol 5, Iss 1, p

    2016  Volume 30

    Abstract: Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop ... ...

    Abstract Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this common infection. In this Review, we discuss how understanding the: (i) molecular and biophysical basis of host-pathogen interactions; (ii) consequences of the molecular cross-talk at the host pathogen interface in terms of disease progression; and (iii) pathophysiology of UTIs is leading to efforts to translate this knowledge into novel therapeutics to treat and prevent these infections.
    Keywords UTI ; rUTI ; CAUTI ; pili ; UPEC ; chaperone-usher pathway (CUP) pili ; Enterococcus ; vaccine ; antibiotic-resistance ; Medicine ; R
    Language English
    Publishing date 2016-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Host restriction of Escherichia coli recurrent urinary tract infection occurs in a bacterial strain-specific manner.

    Valerie P O'Brien / Denise A Dorsey / Thomas J Hannan / Scott J Hultgren

    PLoS Pathogens, Vol 14, Iss 12, p e

    2018  Volume 1007457

    Abstract: Urinary tract infections (UTI) are extremely common and can be highly recurrent, with 1-2% of women suffering from six or more recurrent episodes per year. The high incidence of recurrent UTI, including recurrent infections caused by the same bacterial ... ...

    Abstract Urinary tract infections (UTI) are extremely common and can be highly recurrent, with 1-2% of women suffering from six or more recurrent episodes per year. The high incidence of recurrent UTI, including recurrent infections caused by the same bacterial strain that caused the first infection, suggests that at least some women do not mount a protective adaptive immune response to UTI. Here we observed in a mouse model of cystitis (bladder infection) that infection with two different clinical uropathogenic Escherichia coli (UPEC) isolates, UTI89 or CFT073, resulted in different kinetics of bacterial clearance and different susceptibility to same-strain recurrent infection. UTI89 and CFT073 both caused infections that persisted for at least two weeks in similar proportions of mice, but whereas UTI89 infections could persist indefinitely, CFT073 infections began to clear two weeks after inoculation and were uniformly cleared within eight weeks. Mice with a history of CFT073 cystitis lasting four weeks were protected against recurrent CFT073 infection after antibiotic therapy, but were not protected against challenge with UTI89. In contrast, mice with a history of UTI89 cystitis lasting four weeks were highly susceptible to challenge infection with either strain after antibiotic treatment. We found that depletion of CD4+ and CD8+ T cell subsets impaired the ability of the host to clear CFT073 infections and rendered mice with a history of CFT073 cystitis lasting four weeks susceptible to recurrent CFT073 cystitis upon challenge. Our findings demonstrate the complex interplay between the broad genetic diversity of UPEC and the host innate and adaptive immune responses during UTI. A better understanding of these host-pathogen interactions is urgently needed for effective drug and vaccine development in the era of increasing antibiotic resistance.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 630 ; 572
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: StrainGE

    Lucas R. van Dijk / Bruce J. Walker / Timothy J. Straub / Colin J. Worby / Alexandra Grote / Henry L. Schreiber / Christine Anyansi / Amy J. Pickering / Scott J. Hultgren / Abigail L. Manson / Thomas Abeel / Ashlee M. Earl

    Genome Biology, Vol 23, Iss 1, Pp 1-

    a toolkit to track and characterize low-abundance strains in complex microbial communities

    2022  Volume 27

    Abstract: Abstract Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the ... ...

    Abstract Abstract Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.
    Keywords Metagenomics ; Microbiome ; Strain-tracking ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. 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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  7. Article ; Online: Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection.

    Drew J Schwartz / Matt S Conover / Thomas J Hannan / Scott J Hultgren

    PLoS Pathogens, Vol 11, Iss 1, p e

    2015  Volume 1004599

    Abstract: Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The ... ...

    Abstract Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The mechanism behind this increased risk is unknown; however, bacteriuria increases immediately after sexual intercourse episodes, suggesting that physical manipulation introduces periurethral flora into the urinary tract. In this paper, we investigated whether superinfection (repeat introduction of bacteria) resulted in increased risk of severe UTI, manifesting as persistent bacteriuria, high titer bladder bacterial burdens and chronic inflammation, an outcome referred to as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial replication and is defined histologically by urothelial hyperplasia and submucosal lymphoid aggregates, a histological pattern similar to that seen in humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis after a single infection; however, they developed persistent bacteriuria and chronic cystitis when superinfected 24 hours apart. Elevated levels of interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony-stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second infection predicted the development of chronic cystitis. These same cytokines have been found to precede chronic cystitis in singly infected C3H/HeN mice. Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the proportion of mice that developed chronic cystitis. Intracellular bacterial replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation were essential for this increase. Microarrays conducted at four weeks post inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial peptides during chronic cystitis. These data suggest a mechanism by which caspase-1/11 activation and IL-1 secretion could predispose certain women to recurrent UTI ...
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Host and bacterial proteases influence biofilm formation and virulence in a murine model of enterococcal catheter-associated urinary tract infection

    Wei Xu / Ana L. Flores-Mireles / Zachary T. Cusumano / Enzo Takagi / Scott J. Hultgren / Michael G. Caparon

    npj Biofilms and Microbiomes, Vol 3, Iss 1, Pp 1-

    2017  Volume 12

    Abstract: Urinary tract infections: targeting enzymes might help Identifying bacterial and host enzymes that support biofilm formation may help prevent urinary tract infections caused by catheters. Enterococcus faecalis bacteria is a leading cause of catheter- ... ...

    Abstract Urinary tract infections: targeting enzymes might help Identifying bacterial and host enzymes that support biofilm formation may help prevent urinary tract infections caused by catheters. Enterococcus faecalis bacteria is a leading cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infections. Michael Caparon and colleagues at Washington University School of Medicine in Missouri, USA, studied these infections in mice. They examined the effects of two protein-degrading enzymes, both from the bacterium and one can be activated by urine trypsin-like protease from the animals. Mutations that impaired either one of the enzymes had no effect on the infection, but when both the bacterial enzymes were impaired by mutation the formation of biofilms was significantly reduced. Treating the mice with chemicals that inhibited both bacterial and host enzymes dramatically reduced catheter-induced inflammation and related problems. This suggests drugs targeting these enzymes could be useful in clinical care.
    Keywords Microbial ecology ; QR100-130
    Subject code 572
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Narrowing the spectrum

    Alexandra E. Paharik / Henry L. Schreiber / Caitlin N. Spaulding / Karen W. Dodson / Scott J. Hultgren

    Genome Medicine, Vol 9, Iss 1, Pp 1-

    the new frontier of precision antimicrobials

    2017  Volume 4

    Abstract: Editorial summary Antibiotics have become the standard of care for bacterial infections. However, rising rates of antibiotic-resistant infections are outpacing the development of new antimicrobials. Broad-spectrum antibiotics also harm beneficial ... ...

    Abstract Editorial summary Antibiotics have become the standard of care for bacterial infections. However, rising rates of antibiotic-resistant infections are outpacing the development of new antimicrobials. Broad-spectrum antibiotics also harm beneficial microbial communities inhabiting humans. To combat antibiotic resistance and protect these communities, new precision antimicrobials must be engineered to target specific pathogens.
    Keywords Medicine ; R ; Genetics ; QH426-470
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. 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
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