Upec Vaccine Development: Improving Uti Management Through Prevention
Although it appears that a prior UTI fails to elicit a protective host immune response and uropathogen heterogeneity complicates vaccine design, data from animal model studies offer encouragement for successful UPEC vaccine development . Immunization with UPEC antigens can stimulate a mucosal immune response that may be effective at preventing experimental UTI and increases in urinary and serum antibody titers correlate with reductions in bladder bacterial load and infection duration . With continued effort, these data provide encouragement that an effective UPEC vaccine can be developed.
E Coli And Virulence Factors
Virulence refers to the ability of an organism to cause disease, and is a function of the presence of distinct accessory traits, referred to as virulence factors . VFs are specific properties that enable organisms to overcome host defenses and cause disease . However, although several VFs have been identified in UPEC, experimental and epidemiological data have shown that none uniquely defines these pathogens.
UPEC VFs are grouped by functional categories as adhesins, toxins, iron acquisition systems, and protectins. VFs are encoded by genes located on chromosomes or plasmids, with some being exclusively chromosomal (e.g., pap
Adhesins, which appear as hair-like fibers called fimbriae , facilitate the colonization with E. coli in the urinary tract by attaching to host epithelial cells. This attachment promotes the persistence of the organism in the bladder, and serves as a reservoir for ascending infection in the urinary tract .
Although most studies have confirmed that type 1 fimbriae are particularly important in bladder colonization , the proportions of UPEC strains from urine and feces expressing type 1 fimbriae appear to be similar , ranging from a high of 71% among isolates from cystitis patients to a low of 58% among those from patients with ASB, with fecal strains in the mid-range at 60% . However, in contrast, the level of expression of type 1 fimbriae among UPEC blood isolates is significantly different from that of fecal strains .
Immunizing Via The Intranasal Route Provides The Most Protection Against Uti
We previously established that intranasal immunization followed by two weekly boosts with an outer membrane iron receptor, Hma, IreA, IutA, or FyuA, conjugated to cholera toxin significantly reduced bacterial burden in the bladder or kidneys or both 48h following transurethral challenge with UPEC . We later determined that conjugation of antigen to adjuvant was not required for protection . On the basis of these data, we began systematic optimization of the vaccine to maximize efficacy using alternative adjuvants admixed with antigen. The optimized vaccine route, adjuvant, and antigen were evaluated based on three criteria: reduction of bacterial CFU in the sample sites, increased number of mice without detectable bacterial counts, and production of antigen-specific antibody. Genes encoding all protein antigens were codon optimized, and proteins were purified from inclusion bodies and certified lipopolysaccharide free.
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Symptoms Of Utis In Older People
The classic lower UTI symptoms of pain, frequency, or urgency and upper tract symptoms of flank pain, chills, and tenderness may be absent or altered in older people with UTIs.
Symptoms of UTIs that may occur in seniors but not in younger adults include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath. A preexisting health condition may further confuse the picture and make diagnosis difficult.
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Uropathogen Cocktails: Multistrain Whole
Vaccinating with whole or lysed fractions of inactivated pathogens can be an effective method to generate protective immunity, and a number of successful vaccines against human pathogens, including Bordetella pertussis , Vibrio cholerae and Salmonella Typhi contain killed whole bacteria . There are four standardized whole-cell/cell lysate-based vaccines that have been tried for UTI with limited success .
Urvakol® and Urostim , the third and fourth standardized whole-cell vaccines, are administered as daily oral tablets containing mixtures of inactivated uropathogens. Both formulations contain strains of E. coli, P. mirabilis and E. faecalis, although Urvakol also includes a strain of Pseudomonas aeruginosa, whereas UROstim contains K. pneumoniae. Data from animal and patient studies demonstrate that Urvakol and UROstim have immunostimulating activity as measured by cytokine production and the presence of vaccine-specific antibodies in the serum, urine and saliva of patients after immunization . However, the ability of either vaccine to prevent recurrent UTI has not been established as well-structured clinical trials have yet to be completed.
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Urinary Tract Infections In Babies And Young Children
Babies and children are at risk of UTIs. These infections always need to be investigated as they may indicate a serious underlying condition, such as urinary reflux. Reflux is caused by a bladder valve problem allowing urine to flow back into the kidneys from the bladder. Reflux can cause the urine to stay inside the body increasing the risk of infection. It may lead to kidney scarring, which in turn leads to high blood pressure and sometimes kidney problems.
How Common Are Urinary Tract Infections
Urinary tract infections are very common, occurring in 1 out of 5 women sometime in their lifetime. Though UTIs are common in women, they can also happen to men, older adults and children. One to 2% of children develop urinary tract infections. Each year, 8 million to 10 million visits to doctors are for urinary tract infections.
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Preventive Measures For A Uti
- Drink lots of water.
- Urinate immediately every time after you have sexual intercourse with your partner.
- Dont hold back urine as it may also cause the bacteria to stick.
- Wear cotton panties.
- Have a balanced and nutritious diet.
- Avoid bathing in a bathtub as it may provide a site for the bacteria to grow.
- Avoid douching and scented pads.
- After using the toilet, always wipe in the direction of front to back as this may avoid any germs from getting into the urethral opening.
- Wash your hands properly every time after you use the toilet.
- Avoid alcohol or caffeinated drinks when you are suffering from the UTI.
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Drink Plenty Of Fluids
Stay hydrated throughout the day. This will make you pee more frequently, which flushes bacteria out of your urinary tract.
Water is the best choice. Aim for 6 to 8 glasses per day. If its hard for you to drink that much water, you can also increase your fluid intake by drinking sparkling water, decaffeinated herbal tea, milk, or smoothies made with fruits and vegetables.
Try to limit or avoid alcohol and caffeinated drinks, which may irritate the bladder.
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Prevention Of Recurrent Urinary Tract Infection
Prevention of recurrent UTI has attracted much interest and was investigated by researchers. The European Association of Urology guideline suggests that the prevention of recurrent UTI should include the following in this order: behavioral modifications and avoidance of risk factors, nonantimicrobial measures, and antimicrobial prophylaxis . Due to the limited context, the current review mainly focuses on nonantimicrobial treatment of recurrent UTI.
What Causes Urinary Tract Infections
Normal urine is sterile and contains fluids, salts, and waste products. It does not contain bacteria, viruses, or fungi. A UTI occurs when germs, most often bacteria from the digestive tract, get into the opening of the urethra and start to multiply.
Most UTIs are caused by E. coli bacteria, which normally live in the colon.
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What Conditions Are Related To Recurrent Utis
Recurrent UTIs sometimes happen along with other conditions, such as:
- vesicoureteral reflux , which is found in 30%50% of kids diagnosed with a UTI. In this congenital condition, pee flows backward from the bladder to the ureters. Ureters are thin, tube-like structures that carry pee from the kidney to the bladder. Sometimes the pee backs up to the kidneys. If it’s infected with bacteria, it can lead to pyelonephritis.
- hydronephrosis, which is an enlargement of one or both kidneys due to backup or blockage of urine flow. It’s usually caused by severe VUR or a blocked ureter. Some kids with hydronephrosis might need to take daily low doses of antibiotics to prevent UTIs until the condition producing hydronephrosis gets better or is fixed through surgery.
But not all cases of recurrent UTIs can be traced back to these body structure-related problems. For example, dysfunctional voiding when a child doesn’t relax the muscles properly while peeing is a common cause of UTIs. Not peeing often enough also can also increase a child’s risk for recurrent infections. Both dysfunctional voiding and infrequent urination can be associated with constipation.
Rarely, unrelated conditions that harm the body’s natural defenses, such as diseases of the immune system, also can lead to recurrent UTIs. Use of a nonsterile urinary catheter can introduce bacteria into the urinary tract and also cause an infection.
Uti: A Common & Costly Public Health Burden
Despite the regular flow of urine, formidable physiological barriers and a robust array of host defenses, the human urinary tract remains one of the most common sites for bacterial infection . Approximately half of all women and 12% of men will experience a urinary tract infection in their life-time . Approximately a quarter of these women will have a recurrent infection within 612 months . The high incidence of infection results in 11 million physician office visits and 1.7 million emergency room visits annually in the USA alone . On a population scale, the consequence of frequent UTI amounts to a substantial fiscal public health burden. In 2000, Americans spent a staggering US$3.5 billion treating UTIs .
Urinary tract infection among women is extremely common approximately 13% of women between the ages of 18 and 90 years will have an annual incidence of urinary tract infection
Based on 2010 US census data, an estimated 15 million women will have a UTI annually in the USA . Percentages are proportional to the area of the circles.
UTI: Urinary tract infection.
Classes of uropathogenic Escherichia coli vaccine targets include fimbrial adhesins, surface polysaccharides, outer membrane iron receptors and toxins
LPS: Lipopolysaccharide UPEC: Uropathogenic Escherichia coli.
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Expert Commentary & Five
Although select individual antigen-based UPEC vaccines may successfully prevent experimental infection in animal models, a broadly effective UTI vaccine may need to target more than one virulence factor to be clinically useful against the highly heterogeneous UPEC population. Substantial diversity exists within classes of UPEC virulence factors, such that not every UPEC strain expresses the exact set of virulence-associated genes during infection . Although the genomes of pathogenic E. coli frequently encode many more virulence factors than commensal E. coli strains, the absence of a required core set of virulence factors complicates UTI vaccine design . Targeting a single virulence factor may only be effective against a select group of UPEC strains. Vaccine strategies that target multiple virulence factors, such as the multiepitope vaccines constructed by Wieser and coworkers , provide a solution to the problem of UPEC strain diversity. Through targeting multiple members of a class of virulence factors, such as multiple fimbrial adhesins or multiple iron receptors, rather than an individual, it may be possible to overcome UPEC diversity and design a clinically effective vaccine for UTI.
Iuta Is The Optimal Antigen When Coadministered With Dmlt Via The Intranasal Route
Previous studies with cholera toxin conjugated to antigens found that IreA and IutA provided significant protection from bacterial challenge in the bladder and that Hma, FyuA, and IutA provided protection in the kidneys . When administered via the intranasal route and formulated with dmLT, all four antigens individually trended toward reducing bacterial burdens in the urine .D). In the bladder, CFU counts per gram tissue were significantly reduced compared to administration of adjuvant alone when Hma and IutA were coadministered with dmLT .F). FyuA and IreA did not provide any protection compared to the adjuvant-alone cohort .H). IutA was the only antigen that reduced colonization more than 2-fold in the kidneys, although this reduction was not statistically significant . According to these results, IutA was an effective antigen for reduction of bacterial burden when administered via the intranasal route in combination with dmLT in all sites of infection. In comparison, Hma was an effective antigen in two sites of infection.
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References
The Different Parts Of The Urinary Tract And Those More Prone To Infection
The urinary system is well designed and can often keep E. coli and other types of microscopic invaders at bay. For instance, urinating usually does an excellent job of flushing out lingering bacteria from the urethra before it causes any issues. But when this defense fails, bacteria such as E. coli enters the urinary tract , multiplies, and then a urinary tract infection can develop.
While any part of the urinary tract can be impacted, most E. colicaused UTIs occur in the lower urinary tract, which includes the bladder and the urethra . A UTI that resides in the bladder is called cystitis one that resides in the urethra is called urethritis.
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Does Cranberry Juice Prevent A Urinary Tract Infection
Many people say that cranberry juice can help treat, or even prevent, a UTI. Researchers are currently looking into the topic, but havent found a definitive answer yet. Healthcare providers recommend drinking lots of fluids if you have, or have a history of getting, a UTI. Adding a glass of unsweetened cranberry juice to your diet isnt a proven way to prevent a UTI, but it typically wont hurt you either.
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Tips To Prevent A Urinary Tract Infection
Topics in this Post
A urinary tract infection, also called a UTI, is an infection that occurs in the urinary system. This could include the urethra, bladder, ureters and kidneys. Most infections involve the bladder and urethra, known as the lower urinary tract.
The most common symptoms include painful urination, tenderness above the bladder area, urgency and frequency of urination. Cloudy and a strong odor are not signs of infection.
Women are at greater risk for a UTI because the urethra is shorter than in men, so it’s easier for bacteria to travel to the bladder. UTIs also are more common in postmenopausal women because low estrogen levels change vaginal and urethral tissue to increase the risk of infection.
It’s always better to prevent an infection rather than simply treat it. UTIs are no different.
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When To Contact A Doctor
If a person suspects that they have a UTI, they should ask a healthcare professional for advice about the best way to treat it.
Antibiotics may not always be necessary, but it is still important to seek medical attention. This reduces the risk of developing a more severe infection that is harder to treat.
Below are answers to some frequently asked questions about treating UTIs.
Why Kids Get Urinary Tract Infections
There are a few main reasons kids get UTIs.
You can help your child reduce their risk of developing an infection, just by changing certain behaviors. Here are some suggestions to help your child practice healthy bathroom habits, which in turn, could help prevent infections down the road:
Urinary tract infections are not fun and can be preventable using the suggestions in this blog post. I hope you found this helpful and I encourage you to share this with other parents!
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Antibody Quantification By Elisa
Quantification of antigen-specific antibody concentrations via indirect enzyme-linked immunosorbent assay was performed as previously described . Briefly, 5g/ml purified protein diluted in bicarbonate/carbonate buffer was coated in each well and incubated at 4°C overnight. Plates were washed with PBST using an ELx405 microplate washer and blocked with SuperBlock . Following a second wash in PBST, 50l of sera diluted in SuperBlock or undiluted urine was added to wells and incubated for 1 to 2 h at room temperature. Plates were again washed with PBST and coated with 50l 1:10,000-diluted secondary antibody goat anti-mouse IgG and incubated 1h at room temperature. After a final wash in PBST, 50l 1-Step Ultra TMB was added to each well and incubated at room temperature until sufficient color had developed. To stop the reaction, 50l 2M sulfuric acid was added to each well and the absorbance at 450nm was read with a Quant plate reader . Antibody concentrations were determined by comparing absorbance values to known concentrations of mouse IgG bound to the plate with goat anti-mouse Ig . Serum assays were performed in duplicate for each mouse.