Name: establishment and characterization of uti and cauti in a mouse model
Uploaded: 2015-06-23T15:00:00
Description: Watch this Scientific Journal Video about Establishment and Characterization of UTI and CAUTI in a Mouse Model at JoVE.com

Funding for this work was provided by ORWH SCOR P50 DK064540, RO1 DK 051406, RO1 AI 108749-01, F32 DK 101171, and F32 DK 104516-01.

Ethics statement: The Washington University Animal Studies Committee approved all mouse infections and procedures as part of protocol number 20150226, which expires 12/10/2018. Overall care of the animals was consistent with The Guide for the Care and Use of Laboratory Animals from the National Research Council and the USDA Animal Care Resource Guide. Euthanasia procedures are consistent with the &#8220;AVMA guidelines for the Euthanasia of Animals 2013 edition.&#8221;
1. UPEC UTI Protocol, Inoc...

Uncomplicated community acquired UTI is a common and costly infection accounting for several million primary care visits every year 46. In addition, CAUTIs are a common healthcare acquired infection that has become extremely costly to healthcare providers as the Centers of Medicare and Medicaid Services no longer reimburses providers for the added cost of treatment resulting from hospital acquired CAUTI 45. The mouse models of UTI, both uncomplicated cystitis and CAUTI, described in these protocols ...

An erratum was issued for: <a href="https://www.jove.com/video/52892/establishment-and-characterization-of-uti-and-cauti-in-a-mouse-model">Establishment and Characterization of UTI and CAUTI in a Mouse Model</a>. The Protocol section has been updated.
The ethics statement has been updated from:
Ethics statement: The Washington University Animal Studies Committee approved all mouse infections and procedures as part of protocol number 20120216, which was approved 01/11/2013 and expires 01/11/2016. Overall care of the animals was consistent with The guide for the Care and Use of Laboratory Animals from the National Research Council and the USDA Animal Care Resource Guide. Euthanasia procedures are consistent with the &#8220;AVMA guidelines for the Euthanasia of Animals 2013 edition.&#8221;
to:
Ethics statement: The Washington University Animal Studies Committee approved all mouse infections and procedures as part of protocol number 20150226, which expires 12/10/2018. Overall care of the animals was consistent with The Guide for the Care and Use of Laboratory Animals from the National Research Council and the USDA Animal Care Resource Guide. Euthanasia procedures are consistent with the &#8220;AVMA guidelines for the Euthanasia of Animals 2013 edition.&#8221;
Step 3 has been updated from:
3. Bacterial Inoculation
<ol>
	<li>Clean the workstation with 70% ethanol and cover area with absorbent paper (or use sterile flow hood).</li>
	<li>Draw up to 0.9 ml of the prepared bacterial inoculum into a 1 ml (TB) syringe (remove air bubbles). Attach a prepared sterile inoculation needle with PE10 tubing, onto the syringe containing the inoculum, then sterilely trim the polyethylene tubing. 
	NOTE: Leave 1 mm of tubing above the tip of the needle to avoid puncturing the bladder.</li>
	<li>Cut a 1 inch square piece of parafilm and put a dab of surgical lubricant (approximately the size of a dime) on top.</li>
	<li>Anesthetize female C3H/HeN mice by putting them in a 32 ounce glass jar containing a tea-infuser ball with cotton balls soaked with 3 ml of isoflurane or vaporizer chamber (following manufactures protocol) until unconscious but still breathing normally (1 breath/sec). 
	NOTE: Some IACUC committees do not approve the use of a jar or vaporizer. Please follow the indication of the IACUC committee of your institution. 
	NOTE: If glass jar with tea-ball and/or nose cone with isoflurane-soakd cotton balls are used, the animal must be carefully observed to avoid anesthetic overdose and death. The advantage of using a vaporizer and anesthesia chamber is that it provides controlled isoflurane administration that avoids accidental overdoses. CAUTION: Isoflurane is an inhalation anesthetic. Use in a well-ventilated area and minimize inhalation.</li>
	<li>Remove the mouse from the jar/vaporizer and place it on its back on a paper towel and spread the legs.</li>
	<li>Cover the nose of the mouse with a nose cone (a tube connected to the vaporizer that provides a controlled isoflurance dose that comes equipped on some vaporizer units) or 50 ml conical tube with a cotton ball containing a small amount (approximately 1-2 ml) of isoflurane.</li>
	<li>Gently palpitate the bladder to induce urination and ensure a voided bladder. Wipe the periurethral area with 100% ethanol wipe. Dab the inoculation needle/syringe, point first, into the surgical lubricant.</li>
	<li>Inoculate each mouse with 50 &#181;l of the bacteria solution by inserting the inoculation needle transurethrally, approximately 12 mm, and pressing down on the syringe plunger gently to dispense the inoculum into the bladder gently (10 &#181;l/sec). Remove the inoculation needle from the mouse. 
	NOTE: Immediate return of inoculum at the urethral opening when beginning to inoculate indicates improper or incomplete insertion of the needle.</li>
	<li>Remove the mouse from nose cone and return it to its cage. Repeat steps 3.3-3.8 for each mouse. When/if switching inoculum conditions/strains, dispose of the syringe and inoculation needle in an approved sharps container and start again step 3.2.&#160;&#160; 
	NOTE: Inoculation with uropathogenic organisms generally does not cause severe pain symptoms. However, in rare instances, administering large doses of pathogens may cause fever, reduction in food and water intake and abnormal behavior. Animal health should be monitored throughout the experiment. If overt pain symptoms are notice, an analgesic, such as Buprenorphine (0.05&#8722;0.1 mg/kg given subcutaneously), can be applied. Procedures should be in accordance with each institution&#8217;s IACUC.</li>
</ol>
to:
3. Bacterial Inoculation
<ol>
	<li>Clean the workstation with 70% ethanol and cover area with absorbent paper (or use sterile flow hood).</li>
	<li>Draw up to 0.9 ml of the prepared bacterial inoculum into a 1 ml (TB) syringe (remove air bubbles). Attach a prepared sterile inoculation needle with PE10 tubing, onto the syringe containing the inoculum, then sterilely trim the polyethylene tubing. 
	NOTE: Leave 1 mm of tubing above the tip of the needle to avoid puncturing the bladder.</li>
	<li>Cut a 1 inch square piece of parafilm and put a dab of surgical lubricant (approximately the size of a dime) on top.</li>
	<li>Anesthetize female C3H/HeN mice by putting them in a vaporizer chamber (following manufactures protocol) until unconscious but still breathing normally (1 breath/sec). 
	NOTE: Some IACUC committees do not approve the use of a vaporizer. Please follow the indication of the IACUC committee of your institution. 
	CAUTION: Isoflurane is an inhalation anesthetic. Use in a well-ventilated area and minimize inhalation.</li>
	<li>Remove the mouse from the vaporizer and place it on its back on a paper towel and spread the legs.</li>
	<li>Cover the nose of the mouse with a nose cone (a tube connected to the vaporizer that provides a controlled isoflurance dose that comes equipped on some vaporizer units) to maintain anesthetization.</li>
	<li>Gently palpitate the bladder to induce urination and ensure a voided bladder. Wipe the periurethral area with 100% ethanol wipe. Dab the inoculation needle/syringe, point first, into the surgical lubricant.</li>
	<li>Inoculate each mouse with 50 &#181;l of the bacteria solution by inserting the inoculation needle transurethrally, approximately 12 mm, and pressing down on the syringe plunger gently to dispense the inoculum into the bladder gently (10 &#181;l/sec). Remove the inoculation needle from the mouse. 
	NOTE: Immediate return of inoculum at the urethral opening when beginning to inoculate indicates improper or incomplete insertion of the needle.</li>
	<li>Remove the mouse from nose cone and return it to its cage. Repeat steps 3.3-3.8 for each mouse. When/if switching inoculum conditions/strains, dispose of the syringe and inoculation needle in an approved sharps container and start again step 3.2.&#160;&#160; 
	NOTE: Inoculation with uropathogenic organisms generally does not cause severe pain symptoms. However, in rare instances, administering large doses of pathogens may cause fever, reduction in food and water intake and abnormal behavior. Animal health should be monitored throughout the experiment. If overt pain symptoms are notice, an analgesic, such as Buprenorphine (0.05&#8722;0.1 mg/kg given subcutaneously), can be applied. Procedures should be in accordance with each institution&#8217;s IACUC.</li>
</ol>

An erratum was issued for: <a href="https://www.jove.com/video/52892/establishment-and-characterization-of-uti-and-cauti-in-a-mouse-model">Establishment and Characterization of UTI and CAUTI in a Mouse Model</a>. The Protocol section has been updated.

Erratum: Establishment and Characterization of UTI and CAUTI in a Mouse Model

Urinary tract infections (UTIs) are one of the most common bacterial infections and can be divided into two categories based on the mechanism of acquisition, community and nosocomial acquired UTI. Community-acquired UTIs often occur in otherwise healthy women and studies have shown that approximately 50% of women will have at least one UTI in their lifetime 1. Additionally, recurrence is a major problem. A woman who has an initial acute infection has a 25-40% chance of having a second infection within six months despite appropriate antibiotic treatment and many women continue to have frequent recurrences 2. The bacteria that cause these infections are also becoming increasingly antibiotic resistant further confounding treatment protocols 3-6. UTI affect millions of individuals every year costing approximately 2.5 billion dollars in health care related expenses in the US, underscoring the impact and prevalence of the disease 1,7.Nosocomial acquired UTIs are mainly associated with the presence of foreign bodies such as indwelling catheters. Catheter-associated UTIs (CAUTI) remain the most common nosocomial acquired UTI, accounting for ~70-80% of such infections 8. Furthermore, CAUTI is associated with increased morbidity and mortality and it is the most common cause of secondary bloodstream infections 9.
UPEC associated community acquired UTIs are thought to be caused by the introduction of bacteria into the bladder from reservoirs in the gastrointestinal tract via mechanical manipulation during sexual intercourse, poor hygiene or other microbial population dynamics between different host niches 10. Once inside the bladder, UPEC employ numerous virulence factors, including capsule, iron acquisition systems, toxins, a virulence plasmid, tRNAs, pathogenicity islands and colonization factors that have been shown to play a role in pathogenesis 11-14. Critical to the establishment of UPEC colonization, UPEC also encode multiple types of adhesive chaperone usher pathway (CUP) pili that recognize receptors with stereochemical specificity 15. Type 1 pili, tipped with the FimH adhesin, are expressed by UPEC and bind mannosylated uroplakins 16 and &#945;-1, &#946;-3 integrins 17, which are expressed on the luminal surface of both human and mouse bladders 18. These FimH-mediated interactions facilitate bacterial colonization and invasion of the superficial epithelial cells19,20. Once inside the cell, UPEC can escape into the cytoplasm where a single bacterium can rapidly divide to form an intracellular bacterial community (IBC), which upon maturation, can contain ~104 bacteria 21. IBC formation has been demonstrated in at least six different mouse strains, C3H/HeN, C3H/HeJ, C57Bl/6, CBA, FVB/NJ and BALB/c, and with a wide variety of different UPEC strains and other Enterobacteriaceae 22-24. However temporal and spatial differences of IBC formation can vary depending upon the mouse background and the infecting UPEC strain. In C3H/HeN mice infected with the prototypical UPEC strains UTI89 or CFT073, IBC formation can be visualized as small biomasses of bacteria as early as 3 hpi (hr post infection). This community continues to expand and reaches a &#8220;midpoint&#8221; of development approximately 6 hpi when the rod shaped bacteria occupy a large percentage of the cytoplasmic space of terminally differentiated superficial umbrella cells These early IBCs form in a relatively synchronous manner with the majority displaying similar dimensions and morphologies. ~8 hpi the bacteria in the IBC change from a bacilli to cocci morphology. IBCs are transient in nature. Thus, IBC maturation from 12-18 hpi results in continued expansion of the bacterial population, followed by their filamentation and dispersal out of the cell with subsequent spread to neighboring cells 23. Thus, the IBC niche allows for rapid bacterial growth in an environment protected from host immune responses and antibiotics 25. The distinct stages of UPEC infection that are seen in mice are also observed in humans, such as IBCs and filamentation, supporting the mouse model of UTI as a beneficial tool that can be used to model UTI in humans 22,26-28.
While a majority of women experience a UTI in their lifetime, the outcome of these infections can range from acute self-limiting infection with no recurrence, to frequent recurrent cystitis. Further, studies have shown a strong familial occurrence of UTI, suggesting a genetic component contributes to UTI susceptibility 29. We have found that the differing UTI outcomes seen in clinics can be mirrored by the differing outcomes of experimental UPEC infection among inbred mouse strains 30. For example, C3H/HeN, CBA, DBA, and C3H/HeOuJ mice are susceptible, in an infectious dose-dependent manner, to long-lasting, chronic cystitis characterized by persistent, high titer bacteria (&#62;104 colony forming units (CFU)/ml), high titer bacterial bladder burdens at sacrifice &#62;4 weeks post-infection (wpi), chronic inflammation, and urothelial necrosis . These mice also display elevated serum levels of IL-6, G-CSF, KC, and IL-5 within the first 24 hpi that serve as biomarkers for the development of chronic cystitis. This may accurately represent the natural course of UTI in some women, as placebo studies have shown that a large percentage of women experiencing UTI will retain high levels of bacteria in their urine for several weeks after the first symptoms of cystitis if not given antibiotic treatment 31,32. Further, using C3H/HeN mice, we found that a history of chronic cystitis is a significant risk factor for subsequent severe recurrent infections. Recurrent UTI is the most significant clinical manifestation of UTI and the C3H/HeN mouse is currently the only studied model that recapitulates an increased predisposition after previous exposure. A second UTI outcome is recapitulated in C57Bl/6 mice where acute UPEC infection is self-limiting, with resolution of bladder inflammation and bacteriuria within approximately a week. Interestingly, in this model, UPEC readily form quiescent intracellular reservoirs within the bladder tissue from which UPEC are capable of emerging from a dormant state to reinitiate an active UTI, potentially explaining one mechanism for same strain recurrent UTI in humans 33,34.
In addition to genetic influences on UTI susceptibility, introduction of a catheter into the bladder greatly increases the likelihood of having an infection as well as increasing the range of bacteria able to cause an infection. It has been demonstrated that human urinary catheterization causes histological and immunological changes in the bladder due to mechanical stress that results in a robust inflammatory response, exfoliation, edema of the lamina propria and submucusa, urothelial thinning, and mucosal lesion of the urothelium and kidney 35,36. Additionally, the catheter provides a surface for bacterial attachment thereby creating an environment utilized by several species to cause CAUTI. While UPEC are still a major contributor, Enterococcus faecalis accounts for 15% of these CAUTI 37. E. faecalis is becoming increasingly resistant to antibiotics with vancomycin resistance emergence, posing a serious health concern 38. E. faecalis possess numerous virulence factors including toxins and adhesins necessary for attachment to both the catheter and epithelium 38. During urinary catheterization, the host is vulnerable to microbial adhesion, multiplication and dissemination in the urinary tract 39,40. E. faecalis forms a biofilm on the catheter as part of a mechanism to persist in the bladder and disseminate to the kidneys, which is reproduced in a mouse CAUTI model41. Recently, it has been shown during urinary catheterization, fibrinogen (Fg) is released into the bladder as part of the inflammatory response. Fg accumulates in the bladder, coats the catheter and is essential for E. faecalis biofilm formation, functioning as an attachment scaffold. In a C57BL/6 mouse model of CAUTI, we discovered that E. faecalis biofilm formation on the catheter, and thus persistence in the bladder, was dependent on the Ebp pilus, specifically its tip adhesin EbpA. We found that the N-terminal domain of EbpA specifically binds to Fg coating the catheter. Additionally, it was found that E. faecalis utilizes Fg as metabolite source during infection, thus enhancing biofilm formation 42.
Mouse models have proven critical to understanding as well as predicting clinical manifestations of UTI and CAUTI 41. In this article we demonstrate inoculum preparation of the cystitis UPEC isolate UTI89 and transurethral inoculation of C3H/HeN mice. Additionally, we demonstrate a protocol for catheter insertion in C57BL/6 mice and inoculation of the E. faecalis OG1RF strain. Both of these techniques lead to consistent and reliable UTI or CAUTI in mice. We also display techniques used to observe IBC formation during acute cystitis and urine collection for the analysis of chronic or recurrent cystitis. C3H/HeN mice have been used to study aspects of UPEC pathogenesis including initial bacterial invasion, IBC formation, filamentation and the development of chronic cystitis 23,33,43. These virulence parameters have also been studied in a variety of other mouse backgrounds 22,33. For CAUTI, the C57BL/6 model allows for foreign body implantation into the bladder with subsequent bacterial colonization, which can be maintained for 7 days post infection 41. These models have been useful for assessing bacterial virulence mechanisms, host responses to UTI and mechanisms to subvert host responses, much of which has been subsequently recapitulated or observed in clinical human populations.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Material for catheter and needle preparation:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>30ga needles</td>
			<td>BD Precision Glide</td>
			<td>305106</td>
			<td>30Gx &#189; (0.3 mm x 13mm)</td>
		</tr>
		<tr>
			<td>PE10 polyethylene tubing</td>
			<td>BD</td>
			<td>427400</td>
			<td>Inside diameter -0.011 in (0.28 mm); outside diameter &#8211; 0.024 in (0.61 mm)</td>
		</tr>
		<tr>
			<td>RenaSIL 025 platinum cured silicon tubing</td>
			<td>Braintree Scientific, Inc</td>
			<td>SIL 025</td>
			<td>inside diameter-0.012 x outside diameter 0.025, 25 ft coil</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Material for infections:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Isoflourane &#8211; Isothesia</td>
			<td>Butler Schein</td>
			<td>29405</td>
			<td>250 mL</td>
		</tr>
		<tr>
			<td>Clear Glass Straight-Sided Jar</td>
			<td>Kimble Chase</td>
			<td>5413289V 21</td>
			<td></td>
		</tr>
		<tr>
			<td>Stainless Steel Tea Infuser</td>
			<td>Schefs-Amazon</td>
			<td></td>
			<td>Premium Loose Leaf Tea Infuser By Schefs - Stainless Steel - Large Capacity -</td>
		</tr>
		<tr>
			<td>Non-sterile cotton balls</td>
			<td>Fisherbrand</td>
			<td>22-456-880</td>
			<td></td>
		</tr>
		<tr>
			<td>50 ml Falcon tubes</td>
			<td>VWR</td>
			<td>89039-660</td>
			<td></td>
		</tr>
		<tr>
			<td>Isotec 3 -vaporizer</td>
			<td>Ohmeda</td>
			<td>1224478</td>
			<td></td>
		</tr>
		<tr>
			<td>Ear punch</td>
			<td>Fisher Scientific</td>
			<td>13-812-201</td>
			<td>(when necessary)</td>
		</tr>
		<tr>
			<td>Betadine solution</td>
			<td>Betadine solution</td>
			<td></td>
			<td>10% Povidie-iodine topical solution</td>
		</tr>
		<tr>
			<td>Q-tips</td>
			<td>Fisher Scientific</td>
			<td>22-037-924</td>
			<td>6 in</td>
		</tr>
		<tr>
			<td>Diapers for bench</td>
			<td>Fisherbrand</td>
			<td>14206 63</td>
			<td>Absorbent Underpads (20&#8221;X36&#8221;mats)</td>
		</tr>
		<tr>
			<td>Surgical lubricant</td>
			<td>Surgilube</td>
			<td>0281-0205-36</td>
			<td></td>
		</tr>
		<tr>
			<td>Dissecting scissor</td>
			<td>Fine Science tools, INC</td>
			<td>14084-08</td>
			<td></td>
		</tr>
		<tr>
			<td>Micro-Adson Forceps</td>
			<td>Fine Science tools, INC</td>
			<td>11018-12</td>
			<td></td>
		</tr>
		<tr>
			<td>1 ml syringe</td>
			<td>BD</td>
			<td>309659</td>
			<td>Tuberculin slip tip</td>
		</tr>
		<tr>
			<td>Parafilm</td>
			<td>Bemis</td>
			<td>PM996</td>
			<td>4 in x 125 FT</td>
		</tr>
		<tr>
			<td>Eppendorf rack</td>
			<td>Fisherbrand</td>
			<td>05-541-1</td>
			<td></td>
		</tr>
		<tr>
			<td>Eppendorf tubes</td>
			<td>MIDSCI</td>
			<td>AVX-T-17-C</td>
			<td></td>
		</tr>
		<tr>
			<td>Harvesting catheters, bladders and kidneys:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Homogenizer</td>
			<td>PRO Scientific INC</td>
			<td>Bio-Gen Pro 200</td>
			<td></td>
		</tr>
		<tr>
			<td>5 ml polypropylene round-bottom tube</td>
			<td>BD</td>
			<td>352063</td>
			<td>for organ homogenization</td>
		</tr>
		<tr>
			<td>Paper towel</td>
			<td>Georgia-Pacific</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Pharmco-AAPER</td>
			<td>11100020S</td>
			<td>200 proof</td>
		</tr>
		<tr>
			<td>Costar&#8482; Clear Polystyrene 96-Well Plates</td>
			<td>Corning</td>
			<td>3788</td>
			<td></td>
		</tr>
		<tr>
			<td>1X Phosphate sodium saline</td>
			<td>Sigma-Aldrich</td>
			<td>P3813</td>
			<td></td>
		</tr>
		<tr>
			<td>BRANSONIC Ultrasonic cleaner 1210</td>
			<td>Branson Ultrasonics Corporation</td>
			<td>1210</td>
			<td></td>
		</tr>
		<tr>
			<td>IBC materials:</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>6-well tissue culture test plate</td>
			<td>Techno Plastic Products</td>
			<td>92006</td>
			<td></td>
		</tr>
		<tr>
			<td>Pins</td>
			<td>Fine Science Tools</td>
			<td>26002-20</td>
			<td></td>
		</tr>
		<tr>
			<td>Sylgard 184</td>
			<td>Dow Corning</td>
			<td>3097358-1004</td>
			<td>Silicone Elastomer Kit</td>
		</tr>
		<tr>
			<td>X-gal (5-bromo-4-chloro-3-indolyl-b-D-galactoside)</td>
			<td>Invitrogen</td>
			<td>15520-034</td>
			<td>Ultrapure</td>
		</tr>
		<tr>
			<td>N, N-Dimethylformamide</td>
			<td>Sigma Aldrich</td>
			<td>D4551</td>
			<td></td>
		</tr>
		<tr>
			<td>MgCl2 (Magnesium chloride)</td>
			<td>Sigma Aldrich</td>
			<td>M8266</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium deoxycholate</td>
			<td>Sigma Aldrich</td>
			<td>D6750</td>
			<td></td>
		</tr>
		<tr>
			<td>Nonidet-P40</td>
			<td>Roche</td>
			<td>11754599001</td>
			<td>Octylphenolpoly(ethyleneglycolether)n</td>
		</tr>
		<tr>
			<td>Potassium hexacyanoferrate(II) trihydrate (K-ferrOcyanide)</td>
			<td>Sigma Aldrich</td>
			<td>P3289</td>
			<td></td>
		</tr>
		<tr>
			<td>Potassium hexacyanoferrate(III) (K-ferrIcyanide)</td>
			<td>Sigma Aldrich</td>
			<td>60299</td>
			<td></td>
		</tr>
	</tbody>
</table>

establishment and characterization of uti and cauti in a mouse model

Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. Females are disproportionately afflicted by UTI: 50% of all women will have a UTI in their lifetime. Additionally, 20-40% of these women who have an initial UTI will suffer a recurrence with some suffering frequent recurrences with serious deterioration in the quality of life, pain and discomfort, disruption of daily activities, increased healthcare costs, and few treatment options other than long-term antibiotic prophylaxis. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of community acquired UTI. Catheter-associated UTI (CAUTI) is the most common hospital acquired infection accounting for a million occurrences in the US annually and dramatic healthcare costs. While UPEC is also the primary cause of CAUTI, other causative agents are of increased significance including Enterococcus faecalis. Here we utilize two well-established mouse models that recapitulate many of the clinical characteristics of these human diseases. For UTI, a C3H/HeN model recapitulates many of the features of UPEC virulence observed in humans including host responses, IBC formation and filamentation. For CAUTI, a model using C57BL/6 mice, which retain catheter bladder implants, has been shown to be susceptible to E. faecalis bladder infection. These representative models are being used to gain striking new insights into the pathogenesis of UTI disease, which is leading to the development of novel therapeutics and management or prevention strategies.

The intravesical models of uncomplicated and catheter associated UTI provide flexible platforms for elucidating the molecular mechanisms of bacterial pathogenesis, the impact of these diseases on host tissue, and the development and testing of novel approaches to manage these common and costly infections. Depending on the mouse strain and pathogen, intravesical inoculation can be used to study host-pathogen interactions to elucidate factors necessary for initiating or modulating acute (Figure 1 and <stro...

Watch this Scientific Journal Video about Establishment and Characterization of UTI and CAUTI in a Mouse Model at JoVE.com

Establishment and Characterization of UTI and CAUTI in a Mouse Model

The ability to model urinary tract infections (UTI) is crucial in order to be able to understand bacterial pathogenesis and spawn the development of novel therapeutics. This work&#8217;s goal is to demonstrate mouse models of experimental UTI and catheter associated UTI that recapitulate and predict findings seen in humans.

Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. ...

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Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic ...

Establishment of a Mouse Severe Acute Pancreatitis Model using Retrograde Injection of Sodium Taurocholate into the Biliopancreatic Duct

The prevalence of acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is increasing in younger age groups annually. However, there is a ...

A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) disease that often occurs in premature infants, especially very low birth weight ...

Establishment and Evaluation of a Porcine Vein Graft Disease Model

Venous graft disease (VGD) is the leading cause of coronary artery bypass graft (CABG) failure. Large animal models of CABG-VGD are needed for the ...

Establishment of a Simple and Effective Rat Model for Intraoperative Parathyroid Gland Imaging

Parathyroid gland (PG) identification is a critical unmet need in thyroidectomy. The identification of the PG is challenging in thyroid surgery as it is ...