Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.

Abstract

Catheter-associated urinary tract infections can often lead to secondary bloodstream infections, and catheter-induced bladder inflammation. In this work, authors utilise murine models to probe defective fibrinolysis drives extravascular fibrin formation, potentially predisposing hosts to severe CAUTI.

Related collections

Most cited references 76

Record: found
Abstract: found
Article: not found

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Paul Shannon, Andrew Markiel, Owen Ozier … (2003)

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

0 comments Cited 11127 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

Yingyao Zhou, Bin Zhou, Lars Pache … (2019)

A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.

0 comments Cited 4449 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Urinary tract infections: epidemiology, mechanisms of infection and treatment options.

Ana L. Flores-Mireles, Jennifer N. Walker, Michael Caparon … (2015)

Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.

0 comments Cited 686 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Ana L. Flores-Mireles:

ORCID: http://orcid.org/0000-0003-4610-4246

afloresm@nd.edu

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 27 March 2024

Publication date PMC-release: 27 March 2024

Publication date Collection: 2024

Volume: 15

Electronic Location Identifier: 2704

Affiliations

[1 ]Integrated Biomedical Sciences, University of Notre Dame, ( https://ror.org/00mkhxb43) Notre Dame, IN 46556 USA

[2 ]Department of Biological Sciences, University of Notre Dame, ( https://ror.org/00mkhxb43) Notre Dame, IN 46556 USA

[3 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Molecular Microbiology, , Washington University School of Medicine, ; St. Louis, MO 63110 USA

[4 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Center for Women’s Infectious Disease Research, , Washington University School of Medicine, ; St. Louis, MO 63110 USA

[5 ]W. M. Keck Center for Transgene Research, University of Notre Dame, ( https://ror.org/00mkhxb43) Notre Dame, IN 46556 USA

[6 ]Department of Chemistry and Biochemistry, University of Notre Dame, ( https://ror.org/00mkhxb43) Notre Dame, IN 46556 USA

[7 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Surgery, , Washington University School of Medicine, ; St. Louis, MO 63110 USA

[8 ]Department of Urology, University of Washington Medical Center, ( https://ror.org/00wbzw723) Seattle, WA 98133-9733 USA

[9 ]Department of Pathology and Laboratory Medicine, University of North Carolina, ( https://ror.org/0130frc33) Chapel Hill, NC 27599 USA

[10 ]UNC Blood Research Center, University of North Carolina, ( https://ror.org/0130frc33) Chapel Hill, NC 27599 USA

Author information

Kurt N. Kohler http://orcid.org/0009-0008-3243-0079

Elizabeth R. Lucas http://orcid.org/0009-0002-1478-9324

Andrew Paik http://orcid.org/0009-0004-5622-1096

Wei Xu http://orcid.org/0000-0003-4319-7432

Scott J. Hultgren http://orcid.org/0000-0001-8785-564X

Francis J. Castellino http://orcid.org/0000-0003-0317-9539

Ana L. Flores-Mireles http://orcid.org/0000-0003-4610-4246

Article

Publisher ID: 46974

DOI: 10.1038/s41467-024-46974-6

PMC ID: 10973455

PubMed ID: 38538626

SO-VID: 9d2a1e71-b6a9-4327-a898-81eebb7c1e52

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 17 August 2023

Date accepted : 15 March 2024

Funding

Funded by: FundRef https://doi.org/10.13039/100000062, U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases);

Award ID: R01DK128805

Award ID: R01DK051406

Award Recipient : Ana L. Flores-Mireles

Funded by: FundRef https://doi.org/10.13039/100000060, U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID);

Award ID: R21AI163825

Award ID: U19AI157797

Award Recipient : Ana L. Flores-Mireles

Funded by: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)

Funded by: FundRef https://doi.org/10.13039/100000050, U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI);

Award ID: R01-HL013423

Award ID: U01-HL143403

Award Recipient : Ana L. Flores-Mireles

Funded by: FundRef https://doi.org/10.13039/100000093, U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health);

Award ID: R01-HL160046

Award Recipient : Ana L. Flores-Mireles

Funded by: U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)

Funded by: U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)

Funded by: -Good Venture Foundation/Open Philanthropy Foundation -College of Science’s Paul F. Ware, M.D. Graduate Fellowship

Custom metadata

ScienceOpen disciplines: Uncategorized

Keywords: pathogens,urological manifestations,infection

Data availability:

ScienceOpen disciplines: Uncategorized

Keywords: pathogens, urological manifestations, infection

Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI

Read this article at

Abstract

Abstract

Related collections

Decoding Infection and Transmission

Most cited references 76

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

Urinary tract infections: epidemiology, mechanisms of infection and treatment options.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 117

Most referenced authors 1,527