Indwelling Urinary Catheter Model of Proteus mirabilis Infection

Smith, Sara N.; Armbruster, Chelsie E.

doi:10.1007/978-1-4939-9601-8_17

Cited by 10 publications

(8 citation statements)

References 7 publications

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“… P. mirabilis strain HI4320 was isolated from the urine of an elderly female nursing home patient with a long-term (≥30 days) indwelling catheter ( 26 , 44 ). This strain is well established as a model organism for P. mirabilis virulence studies and readily produces experimental UTIs in mice ( 23 , 45 , 46 ). Escherichia coli S17λpir/pSAM_AraC was used as the donor strain for mating (Addgene 91569) ( 30 ).…”

Section: Methodsmentioning

confidence: 99%

Construction of an Ordered Transposon Library for Uropathogenic Proteus mirabilis HI4320

et al. 2022

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Section: Methodsmentioning

confidence: 99%

Construction of an Ordered Transposon Library for Uropathogenic Proteus mirabilis HI4320

et al. 2022

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“…Our group and others have successfully enumerated genetic bottleneck effects observed in the traditional model of ascending UTI (6,21,22). Although relatively generous infection dynamics of P. mirabilis in mice have been estimated for a murine model where a catheter segment is entirely inserted into the bladder lumen (18,19), we found the bottleneck for P. mirabilis is narrow in the traditional UTI model and would therefore be problematic for large screening experiments in vivo (Fig. 1).…”

Section: Resultsmentioning

confidence: 88%

“…Previous studies on P. mirabilis virulence have relied on a well-established murine model of UTI (15). Most often, this model involves instillation of bacteria directly into the bladder via a catheter, which can either be removed to study UTI progression in the absence of a foreign body, or fully pushed into the bladder to model long-term catheterization (16)(17)(18). In either case, P. mirabilis readily establishes infection and, similar to human UTI, may cause pyelonephritis and urolithiasis (15).…”

Section: Introductionmentioning

confidence: 99%

Organ agar serves as physiologically relevant alternative for in vivo colonization

Pearson

Shea

Smith

et al. 2023

Preprint

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Animal models for host-microbial interactions have proven valuable, yielding physiologically relevant data that may be otherwise difficult to obtain. Unfortunately, such models are lacking or nonexistent for many microbes. Here, we introduce organ agar, a straightforward method to enable the screening of large mutant libraries while avoiding physiological bottlenecks. We demonstrate that growth defects on organ agar were translatable to colonization deficiencies in a murine model. Specifically, we present a urinary tract infection agar model to interrogate an ordered library of Proteus mirabilis transposon mutants, with accurate prediction of bacterial genes critical for host colonization. Thus, we demonstrate the ability of ex vivo organ agar to reproduce in vivo deficiencies. This work provides a readily adoptable technique that is economical and uses substantially fewer animals. We anticipate this method will be useful for a wide variety of microorganisms, both pathogenic and commensal, in a diverse range of model host species.

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“…We therefore sought to determine the contribution of E. faecalis L-ornithine secretion and P. mirabilis arginine biosynthesis to the successful establishment of polymicrobial catheter biofilms as well as promoting dissemination to the kidneys and bloodstream and overall disease severity. To address this hypothesis, we utilized the E. faecalis arcD mutant and the P. mirabilis argF mutant to examine the specific contribution of ornithine export and arginine biosynthesis to pathogenesis in the well-established murine CAUTI model (35,40,41). Female CBA/J mice aged 6-8 weeks were transurethrally inoculated with 10 5 CFUs of either wild type P. mirabilis, the argF mutant, wild-type E. faecalis, the arcD mutant, or polymicrobial mixtures, and a 4mm silicone catheter segment was placed in the bladder during inoculation.…”

Section: L-ornithine Secretion By E Faecalis and L-arginine Biosynthe...mentioning

confidence: 99%

Metabolic interplay betweenProteus mirabilisandEnterococcus faecalisfacilitates polymicrobial biofilm formation and invasive disease

Hunt

Brix

Vath

et al. 2023

Preprint

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Catheter-associated urinary tract infections (CAUTI) account for 40% of all nosocomial infections and can lead to significant life-threatening complications such as bacteremia. Microbial biofilms play an important role in the development and pathogenesis of CAUTI, and these biofilms are often polymicrobial. Proteus mirabilis and Enterococcus faecalis are two of the most common causes of CAUTI, and they often persistently co-colonize the catheterized urinary tract. We previously demonstrated that co-culture of E. faecalis with P. mirabilis increased biofilm biomass, antimicrobial resistance, and disease severity. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution of this polymicrobial interaction to CAUTI severity. Though compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared to single-species biofilms. By testing mutants of E. faecalis and P. mirabilis, we found that L-ornithine secreted by the E. faecalis ArcD antiporter promotes L-arginine biosynthesis in P. mirabilis via ArgF, which ultimately fuels production of proteins that facilitate contact-dependent interactions to enhance biofilm biomass. We further demonstrate that ArcD and ArgF are not important for urinary tract colonization by either species when alone, but ornithine/arginine interplay is critical for the increased disease severity that occurs during coinfection. This study provides deeper insight into the polymicrobial interactions occurring during CAUTI and highlights how these interactions can have significant impacts on pathogenesis and bacterial persistence.

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Indwelling Urinary Catheter Model of Proteus mirabilis Infection

Cited by 10 publications

References 7 publications

Construction of an Ordered Transposon Library for Uropathogenic Proteus mirabilis HI4320

Construction of an Ordered Transposon Library for Uropathogenic Proteus mirabilis HI4320

Organ agar serves as physiologically relevant alternative for in vivo colonization

Metabolic interplay betweenProteus mirabilisandEnterococcus faecalisfacilitates polymicrobial biofilm formation and invasive disease

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