A release from the European Society of Clinical Microbiology and Infectious Diseases notes that symptoms of a urinary tract infection (UTI) such as cystitis are common in women but, in around a quarter of cases, no infection is found using standard testing.

The research team in Belgium used a more sensitive test and found evidence of bacterial infection in almost all women with UTI symptoms, including those where no bacteria were found with standard testing.

The study, led by Dr Stefan Heytens,supports the idea that testing is unnecessary for women with symptoms of an uncomplicated UTI.

UTI symptoms account for between two and five per cent of women’s GP appointments. In 60-80% of cases, urine testing reveals a bacterial infection.

Testing involves using laboratory techniques to detect bacteria in the urine.

These women may be offered antibiotics such as nitrofurantoin, trimethoprim or fosfomycin.

However, doctors have assumed that women with negative tests do not have a bacterial infection. In the past, this group of women may have been diagnosed with unexplained “urethral syndrome”, which some researchers have suggested could be psychosomatic.

Dr Heytens, who is a practicing GP and a researcher at the department of family medicine and primary health care at the University of Ghent, explained: “A substantial percentage of women visiting their GP with symptoms of a UTI, who test negative for a bacterial infection, are told they have no infection and sent home without treatment.

“On the other hand, women with a positive test might be given a short course of antibiotics to treat their infection.”

The new research involved 308 Belgian women, including 220 who were visiting their GP for UTI symptoms and 86 healthy volunteers. All the women gave urine samples.

Urine samples were tested in the standard way to see whether any bacteria grew. They were also tested using a technique called quantitative polymerase chain reaction, or qPCR. This technique is very sensitive and can be used to detect tiny quantities of DNA that come from bacteria which can cause UTIs, such as Escherichia coli (E. coli) and Staphloccocus saprophyticus (S. saphrophyticus).

Among the women with UTI symptoms, standard testing detected bacteria in 80.9% of urine samples. But the qPCR test found evidence of E. coli in 95.9% of samples and S. saphrophyticus in 8.6%. Combining the results of both tests found evidence of an infection in 98.2% of women with symptoms.

In the women without symptoms, standard testing picked up E. coli in 10.5% of samples and qPCR picked up E. coli in 11.6%.

Dr Heytens said: “In this study, we used a more sensitive test to look for bacteria that commonly cause UTIs. We found E. coli in nearly all women complaining of symptoms, even if they had a negative traditional urine culture. This suggests that if a woman has these symptoms, she probably does have a UTI.

“Our findings support previous research which indicates that traditional testing may not be helpful in uncomplicated UTIs. However, traditional urine culture tests may still have a role to play if treatment fails or if there are signs and symptoms of a more complicated UTI.

“What we don’t yet know is whether all women with these symptoms would benefit from a course of antibiotics.”

Dr Heytens says the findings need to be confirmed in further research. He and his colleagues also plan to investigate whether women with UTI symptoms but a negative urine test would benefit from treatment with antibiotics, and whether they can use qPCR to detect other types of bacteria which might be causing UTIs in rarer cases.

A new study done at Duke University has shown that a protein called HipA acts as a kind of molecular Sandman, putting bacterial cells to sleep so they can live another day. The researchers behind the finding say understanding HipA may give them a way to combat drug-tolerant infections.

Their research, published July 29th 2015 in Nature, found that particularly potent, mutant versions of HipA cause multidrug tolerance in urinary tract infections. It explains how these mutations boost the protein’s slumberous powers to help more bacterial cells avoid being obliterated by antibiotics.

A release from the university quotes Richard G. Brennan, Ph.D., professor and chair of biochemistry at Duke University School of Medicine, as saying, “This discovery presents us with a new method for combating multidrug tolerance. If we can find a way to block this protein, we may be able to awaken these problematic cells or keep them from falling asleep in the first place, so that we can eliminate them for good.”

Multidrug tolerance occurs when a disease-causing microorganism manages to survive or tolerate an onslaught of antibiotics or other antimicrobials. It is not to be confused with the related phenomenon multidrug resistance, where pathogens alter their genetic makeup to become resistant to specific drugs. In multidrug tolerance, microbes instead change their behavior, temporarily shutting down cellular functions that are the typical targets of drugs so they are not seen as a threat.

Because only about one in a million bacterial cells employs this tactic, it is particularly difficult to decipher how these so-called “persisters” are able to emerge. More than three decades ago, researchers studying the common bacteria E. coli found that a protein called HipA was responsible for driving cells into dormancy. Studies showed that a mutated version of HipA, called HipA7, could generate 1000 times as many persisters.

Despite these advances, it still wasn’t clear whether the HipA protein played a role in human disease. To investigate this possibility, the Duke researchers and their collaborators at Northeastern University sequenced the hipA gene of multiple E. coli samples from patients with urinary tract infections. They found that nearly two dozen of the samples harbored the hipA7 “high persister” mutations, which they then showed were responsible for causing recurrent infections in patients.

Oddly enough, the mutations were found to reside far from the part of the protein responsible for flipping the switch make a cell dormant. HipA acts as a kind of signaling protein, ordering other proteins to do the dirty work of driving dormancy. It has to be rather selective about sending out these signals or else all the bacteria will become catatonic. Therefore, HipA spends most of its time inactive, locked tightly in a complex with DNA and its partner protein HipB.

To see if they could explain the impact of the hipA7 mutations, the Duke team used x-ray crystallography to produce an atomic-level three-dimensional structure of the larger complex. When HipA is active in signaling, it appears as a single molecule or monomer. But they found that when it is bound in a complex with HipB and DNA to be quiet, it pairs up, or dimerizes, with another copy of itself. These dimers lock the complex into place, while also blocking HipA’s active site. Because the hipA7 mutations are located where the two copies of the protein come together, they essentially keep the dimers from forming properly.

“It suddenly all made sense,” said Maria A. Schumacher, Ph.D., lead study author and professor of biochemistry at the Duke University School of Medicine. “The protein is normally kept inactivated in this tight complex, but when it is set free, then and only then will it be activated. These mutations make it easier for HipA to be released so it can wreak havoc and promote persistence.”

Now that the researchers understand how this structure enables cells to persist and outlast antibiotics, they can begin to explore new therapies that target this specific mechanism of multidrug tolerance. Brennan and Schumacher are currently searching for molecules that can keep HipA inactive so that it can no longer switch bacterial cells into sleep mode.

The research findings reveal the specific genes expressed by Escherichia coli, the bacteria that most often causes UTIs in otherwise healthy people. The study was published in December 2014 in Proceedings of the National Academy of Sciences

A release from the university quotes senior study author Harry T. Mobley, Ph.D. as saying, “The bacterium is becoming resistant to currently available antibiotics, making it imperative to develop new treatment and prevention strategies. The next logical step is to identify and develop therapies that selectively block these UTI-specific genes.”

In the study of 42 women, 7.7 percent had infections that were resistant to ciprofloxacin and 15.3 percent did not respond to trimethoprim/ sulfamethoxazole, two antibiotics commonly used for treatment.

The U-M team used genomic screening tools to take a deeper look at the mechanisms for infection. Rather than the expected virulence factor, the newly discovered E. coli-specific genes helped protect the bacterial species from the toxic effect of metal ions the body uses to fight infection.

Attacking this function, and other mechanisms that promote survival of the bacteria in the urinary tract, may be a strategy for new microbial agents, the authors say.