Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures

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

doi:10.1016/j.juro.2016.01.100

Cited by 81 publications

(138 citation statements)

References 25 publications

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“…The deposition of other host matrix proteins, including fibronectin and elastin, on prostheses is known to promote bacterial adhesion and facilitate persistent infection (39). Here we also show that S. aureus (i) exploits Fg deposition during a mouse CAUTI model via ClfB interactions and (ii) specifically colocalizes with Fg deposited on catheters from patients with S. aureus-positive cultures, despite the patients receiving appropriate, intensive antibiotic therapy (27). This suggests that an approach that can disrupt or prevent interaction with Fg may be developed as an antibiotic-sparing therapy.…”

Section: Discussionsupporting

confidence: 56%

“…We found that Fg was deposited on all patient catheters and S. aureus colocalized with deposited Fg (Fig. 5), despite receiving intensive antibiotic therapy (27) (Table S2). Together, these data indicate that Fg deposition on urinary catheters alters the UT environment, making it more suitable for MRSA adherence and persistent colonization.…”

Section: Catheterization Creates a Permissive Environment For Mrsa Urmentioning

confidence: 88%

“…catheter, which induces the release of host proteins, including Fg (26,27,36). In the mouse model, the proinflammatory profile upon catheterization was dominated by the up-regulation of IL-6, which is involved in the induction of Fg expression and potentiation of its release into the bladder lumen (26,38,(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

“…To investigate whether Fg or S. aureus could be detected on human urinary catheters, patients 18 y or older in the Urology Department at Washington University School of Medicine undergoing catheterization were consented and enrolled in our study. The dwell time, urine culture, and antibiotics prescribed were recorded for each patient (Table S2) as previously published (27). The Washington University School of Medicine Internal Review Board approved this study (approval 210410058) (see SI Materials and Methods for more details on each catheter used in this study).…”

Section: Methodsmentioning

confidence: 99%

“…Further, urinary catheters removed from humans have been shown to be coated with Fg (27). It has long been recognized that…”

mentioning

confidence: 99%

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Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract

Walker

Flores-Mireles

Pinkner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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103

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Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual's susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus. Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA-Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB − strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host's robust immune response.host-pathogen interactions | MRSA CAUTI | ClfB-fibrinogen interactions

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Section: Discussionsupporting

confidence: 56%

Section: Catheterization Creates a Permissive Environment For Mrsa Urmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Further, urinary catheters removed from humans have been shown to be coated with Fg (27). It has long been recognized that…”

mentioning

confidence: 99%

See 3 more Smart Citations

Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract

Walker

Flores-Mireles

Pinkner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

103

164

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A Readily Scalable, Clinically Demonstrated, Antibiofouling Zwitterionic Surface Treatment for Implantable Medical Devices

et al. 2022

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conditions to maintain the scale of medical device manufacturing; and 4) the treatment must not incorporate antibiotics to maintain global antimicrobial stewardship efforts. The zwitterionic polymer polysulfobetaine (PSB) was selected as the antifouling component of the surface modification to benefit from its biocompatibility, ultralow-fouling properties, and oxidative stability. By adsorbing water electrostatically, PSB coatings form a thin hydration barrier that prevents organic materials from adhering to surfaces. [22] Commonly used approaches to attach PSB coatings to surfaces, such as radical-initiated graft polymerizations of PSB-methacrylate necessitate the use of oxygen-free conditions, [23] preconditioning steps, [24] or long reaction times [25] that do not meet scalability requirements. To circumvent the use of air-free graft polymerizations, we employ perfluorophenylazide (PFPA) chemistry as a molecular anchor to link the PSB coatings onto the surfaces of polymeric materials under ambient conditions. When triggered with UV-light, PFPA moieties generate a highly reactive nitrene that forms covalent bonds with materials containing amines, CC double bonds, and CH bonds. [26,27] With this method, PSB is rapidly coated onto a broad range of substrates using UV light under ambient conditions with no preconditioning steps. Thus, many different medical devices may be quickly and conveniently treated on the manufacturing level.We first demonstrate the effect of the treatment on polydimethylsiloxane (PDMS) as an exemplary, extremely difficultto-modify model for a common elastomer used in implantable medical devices. [28] Commonly known as silicone, PDMS is widely used for its biocompatibility, good chemical stability, ease of fabrication using injection molding or extrusion, and low cost. [29][30][31] Many implantable device makers have moved away from classical medical elastomers and plastics such as latex and polyvinyl chloride due to allergens [32] or plasticizers [33] in these materials that leach out and often lead to irritation or complications. PDMS-based devices do not require plasticizers and have been shown to lead to fewer complications than latex and polyurethane-based devices. [34] Despite its ideal properties, the nonpolar nature of PDMS facilitates the adhesion of organic materials. Bacteria, platelets, proteins, and other biomolecules bind strongly to the hydrophobic surfaces of PDMS elastomers, leading to the colonization and proliferation of biofilms. [22] When common hydrophilic surface treatments are performed on PDMS, such as plasma oxidation, [35] UV-ozone, [36] or corona discharge, [37] the effects are short-term due to rapid hydrophobic recovery. The highly mobile chains of PDMS (glass transition temperature ≈ −120 °C) can reorient themselves to "hide" the surface modified elastomers, when exposed to air, within hours. [38] Other methods seeking long-lasting hydrophilic PDMS surfaces typically require preconditioning steps with silane [39][40][41] chemistry or radical polymerization. [...

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Tackling catheter‐associated urinary tract infections with next‐generation antimicrobial technologies

Duque‐Sanchez,

Qu,

Voelcker

et al. 2023

J Biomedical Materials Res

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Urinary catheters and other medical devices associated with the urinary tract such as stents are major contributors to nosocomial urinary tract infections (UTIs) as they provide an access path for pathogens to enter the bladder. Considering that catheter‐associated urinary tract infections (CAUTIs) account for approximately 75% of UTIs and that UTIs represent the most common type of healthcare‐associated infections, novel anti‐infective device technologies are urgently required. The rapid rise of antimicrobial resistance in the context of CAUTIs further highlights the importance of such preventative strategies. In this review, the risk factors for pathogen colonization in the urinary tract are dissected, taking into account the nature and mechanistics of this unique environment. Moreover, the most promising next‐generation preventative strategies are critically assessed, focusing in particular on anti‐infective surface coatings. Finally, emerging approaches in this field and their likely clinical impact are examined.

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Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures

Cited by 81 publications

References 25 publications

Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract

Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract

A Readily Scalable, Clinically Demonstrated, Antibiofouling Zwitterionic Surface Treatment for Implantable Medical Devices

Tackling catheter‐associated urinary tract infections with next‐generation antimicrobial technologies

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