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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: 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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  4. Article ; Online: Metabolic Requirements of Escherichia coli in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis

    Matt S. Conover / Maria Hadjifrangiskou / Joseph J. Palermo / Michael E. Hibbing / Karen W. Dodson / Scott J. Hultgren

    mBio, Vol 7, Iss 2, p e00104-

    2016  Volume 16

    Abstract: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent ... ...

    Abstract Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly, lacZ was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZ strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a galK mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene yeaR revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies.
    Keywords Science ; Q ; Microbiology ; QR1-502
    Subject code 572
    Language English
    Publishing date 2016-04-01T00:00:00Z
    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: Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions

    Caitlin N Spaulding / Henry Louis Schreiber IV / Weili Zheng / Karen W Dodson / Jennie E Hazen / Matt S Conover / Fengbin Wang / Pontus Svenmarker / Areli Luna-Rico / Olivera Francetic / Magnus Andersson / Scott Hultgren / Edward H Egelman

    eLife, Vol

    2018  Volume 7

    Abstract: Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold ... ...

    Abstract Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.
    Keywords Chaperone-usher pathway pili ; CUP pili ; type 1 pili ; cryo-EM ; UPEC ; UTI ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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