• Escherichia coli bacteria are responsible for 80% of community-acquired urinary tract infections (UTIs).
• Over 40% of individuals experience recurrent UTIs; of these, 10-25% are due to antibiotic-resistant bacteria.
• A recent study found that vaccines based on a metal-organic framework demonstrate a strong immune response in mice.
• Vaccinated mice survived typically lethal doses of E. coli.
• Vaccinated mice demonstrated an increase in the tissue responsible for producing long-lived antibody-secreting cells.

Antibacterials, also known as antibiotics, treat and prevent diseases caused by bacteria. However, their widespread misuse has led to some bacteria evolving resistance, which is called antibiotic resistance.

The World Health Organization (WHO) says “Antibiotic resistance is one of the biggest threats to global health, food security, and development today. [It] leads to longer hospital stays, higher medical costs, and increased mortality.”

The impact of UTIs

UTIs are one of the most common bacterial infections. At least half of all women and 12% of men will have at least one UTI in their lifetime.

UTIs occur when bacteria enter the urinary tract. E.coli, which belongs to the Enterobacteriaceae family of Gram-negative bacteria, are responsible for 80% of community-acquired UTIs. The WHO considers resistant Enterobacteriaceae to be a critical priority.

Medical News Today spoke with the corresponding author of a recent paper Jeremiah Gassensmitt, Ph.D., an associate professor of chemistry and biochemistry at the University of Texas at Dallas; he said:

“You’ll find people thinking this is a disease of inconvenience, but the truth is that women with recurrent UTI routinely have to [choose] between dying or losing their bladder. The disease is terrible, and antibiotic resistance has made it largely incurable.”

UTIs are linked with greater morbidity and mortality and often need longer courses of antibiotics in an attempt to resolve the infection. More than 40% of individuals experience recurrent infection.

According to the authors of the recent paper, studies have shown that 10–25% of people with a UTI have contracted an infection with bacteria that are resistant to the most common antibiotic treatment: trimethoprim and sulfamethoxazole.

This failure of antibiotic treatment means the bacteria stay in the bladder. If left untreated, they can travel to the kidneys and into the bloodstream, leading to kidney infection (pyelonephritis) and urosepsis, a type of sepsis that has mortality rates of 30–40%.

Whole-cell approach

Scientists have investigated various methods to develop a vaccine against bacterial infection; the so-called whole-cell approach has shown promising results. Scientists have based this method on the use of whole inactivated bacteria.

However, inactivated whole-cell bacterial vaccines only cause a weak immune response because the body removes the cells quickly.

A recent study, which appears in ACS NANO, investigated a new way to deliver the whole inactivated bacterial cell into the body to overcome the need for high doses and associated short-term immunity.

In the study, the researchers trapped inactivated E. coli bacteria in a biodegradable shell made up of a “metal-organic framework.”

“We have found a way to take something that’s not infectious… or even alive… and make it mimic the life span of an actual infection by putting it in a slow-release depot made of metal-organic frameworks,” said Dr. Gassensmith.

The scientists injected inactivated E.coli either trapped in a metal-organic framework or a saline solution under the skin of mice and observed them for 12 days. Researchers found that the trapped E. coli stayed at the injection site for 4 days longer than the saline or non-trapped E. coli.

They went on the measure the levels of antibodies associated with the different formulations. The trapped E. coli produced higher levels of anti-E. coli immunoglobulin (IgG) antibodies compared with the E. coli in saline solution.

In an extended study, the scientists gave the mice a lethal dose of E. coli. Only the vaccinated mice survived. The scientists hypothesized that it was due to the 5-fold increase in serum levels of IgG antibodies in these mice.

Mice that had received a vaccination also demonstrated an increase in the tissue responsible for producing long-lived antibody-secreting cells. These cells have associations with protection against infection and long-term antibody-based immunity.

Future applications

According to Dr. Gassensmith, “the use of a ‘slow release’ depot that better mimics the course of a natural infection is difficult with vaccines. […] most vaccines are made from proteins that wouldn’t survive very long sitting in a little pocket under the skin waiting to be released over a week.”

“Foreign proteins are usually dealt with very quickly by the immune system,” he continued, “and when the immune system can take care of something really quickly, it doesn’t make the antibodies and direct a strong cell response —why would it? That’s just extra energy it clearly doesn’t need to expend.”

In the interview with MNT, Dr. Gassensmith explained that the team “believe strongly that our approach is translatable beyond bacterial infection […] we have found a way to safely let vaccines hang out for a while and slowly be made available to the immune system.”

Lead author Dr. Nicole De Nisco echoed this, saying:

“This study on UTI was a proof of concept that whole-cell vaccines are more effective in this extreme, lethal-sepsis model. Showing that this works against recurrent UTI would be a significant breakthrough.”

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