Original Source: http://www.kashmirmonitor.in/news-new-device-to-improve-urinary-infections-treatment-90876.aspx
Urinary tract infections could be treated more quickly and efficiently using a DNA sequencing device the size of a USB stick, says a study.
“We found that this device, which is the size of a USB stick, could detect the bacteria in heavily infected urine – and provide its DNA sequence in just 12 hours. This is a quarter of the time needed for conventional microbiology,” said one of the researchers Justin O’Grady from University of East Anglia in England.
The new device called MinION detected bacteria from urine samples four times more quickly than traditional methods of culturing bacteria.
The new method can also detect antibiotic resistance – allowing patients to be treated more effectively, the researchers said.
“Swift results like these will make it possible to refine a patient’s treatment much earlier – and that is good for the patient, who gets the ‘right’ antibiotic,” O’Grady said.
“This technology is rapid and capable not only of identifying the bacteria in UTIs (urinary tract infections), but also detecting drug-resistance at the point of clinical need,” O’Grady noted.
Professor David Livermore from University of East Anglia’s Norwich Medical School explained that urinary tract infections are among the most common reasons for prescribing antibiotics.
“Antibiotics are vital, especially if bacteria has entered the bloodstream, and must be given urgently. But unfortunately it takes two days to grow the bacteria in the lab and test which antibiotics kill them,” Livermore noted.
As a result, doctors must prescribe a broad range antibiotics, targeting the bacteria most likely to be responsible, and then adjust treatment once the lab results come through, he pointed out.
“This ‘carpet-bombing’ approach represents poor antibiotic stewardship, and it is vital that we move beyond it. The way to do so lies in accelerating laboratory investigation, so that treatment can be refined earlier, benefitting the patient, who gets an effective antibiotic, and society, whose diminishing stock of antibiotics is better managed,” Livermore said.
The findings were presented at an international medical conference run jointly by the American Society for Microbiology’s Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) and the International Society of Chemotherapy (ICC) at San Diego in the US.
Duke Medicine researchers have found that bladder cells have a highly effective way to combat E. coli bacteria that cause urinary tract infections (UTIs).
In a study published online May 28, 2015, in the journal Cell, Duke researchers and their colleagues describe how bladder cells can physically eject the UTI-causing bacteria that manage to invade the host cell.
This response is analogous to having indigestion and vomiting to rid the stomach of harmful substances.
The finding suggests there may be a potential way to capitalize on this natural tendency in bladder cells to help treat recurring UTIs.
UTIs are the second most common type of infection in the body, accounting for about 8.1 million doctor visits annually, the majority of which occur in women, according to the National Institutes of Health. Bacterial infections are the most common cause of UTIs, with 70 percent of infections arising from a particular type of E. coli bacteria.
“The cost for managing UTIs in the U.S. is close to $3 billion annually,” said senior author Soman Abraham, Ph.D., professor in the departments of Pathology, Immunology, and Microbiology and Molecular Genetics at Duke University School of Medicine, and professor in the Program in Emerging Infectious Diseases, Duke-National University of Singapore.
“Because E. coli are able to hide inside of the bladder cells, it’s especially difficult to treat UTIs with regular antibiotics,” Abraham said. “So there is increased need to find new strategies for treatment, including co-opting any preexisting cellular tactics to combating infection.”
When E. coli first attack bladder cells, the cell’s surveillance machinery—known as autophagy—is the first line of defense against pathogens. The autophagy machinery encases the bacteria in a host membrane and shuttles them to the lysosome, a “capsular cauldron,” that destroys harmful pathogens in its acidic environment. But upon entering the lysosome, some pathogens have the capacity to neutralize the acidic environment and avoid being degraded.
Using mouse models of UTIs and cultured human bladder cells, the authors found that the host cells can sense when lysosomes have been rendered neutral and are malfunctioning. The host cells then respond by triggering the lysosome to eject its contents, including the bacteria.
“When the cells have trouble digesting the materials in the lysosomes, a logical way to get rid of this potential hazard is to throw it up,” said first author Yuxuan Miao, a Ph.D. candidate in Duke’s department of Molecular Genetics and Microbiology.
The bacteria that are expelled out of the bladder cells appear to be encased in a cell membrane, presumably ensuring their elimination in urine and avoiding any bacterial reattachment to the bladder wall.
“It was thought that lysosomes always degrade their contents,” Miao said. “Here we are showing for the first time that when the contents cannot be degraded, the lysosome appears to have a back-up plan which is to expel the contents in capsules.”
The researchers hope these findings will aid in finding chemical targets that can accelerate and amplify the bladder cell’s ability to expel the bacteria.
“A lot of women tend to experience recurrent infections once they have an initial bout of UTI,” Abraham said. “The reason for this is that there is bacterial persistence within the cells of the bladder. If we can eliminate these reservoirs using agents that promote expulsion, then we can potentially eradicate recurrent UTIs.”
Most of us think of bacteria as the enemy, but each of our bodies harbors trillions of microbes, most of them beneficial or benign. Now, you can add two new friendlies to the list. This week, two groups of synthetic biologists seeking to repurpose living microbes for human benefit report genetically modifying bacteria to detect cancer in mice and diabetes in humans.
Clinicians have sought to exploit microbes for more than a century. Beginning in 1891, an American bone surgeon named William Coley injected more than 1000 patients with bacterial colonies in hopes that they would shrink inoperable tumors. The treatment sometimes worked, in part because the microbes preferentially seek out tumor tissue, which is rich in nutrients yet has few immune cells to knock out any pathogens. But the results were uneven, and with the rise of radiation and chemotherapy, the approach fell out of favor. More recently, synthetic biologists have begun to modify bacteria to fight cancer and other diseases—engineering them to secrete toxins inside tumors, for example. A couple of these therapies have even made it into clinical trials, though none have been approved yet.
Far less effort has been directed at using bacteria as a test for disease. Sangeeta Bhatia, a biomedical engineer at the Massachusetts Institute of Technology (MIT) in Cambridge, and her colleagues previously worked on cancer detection using metal nanoparticles. In the presence of a tumor, the particles would release snippets of proteins called peptides that could be detected in the urine. Unfortunately, Bhatia says, the signal was often too weak to serve as a clear indicator of disease. Bhatia’s team then realized that bacteria offered a potentially superior option. The researchers knew that microbes with a taste for tumor often penetrate the masses as they grow and replicate. So Bhatia’s group joined up with a team led by Jeff Hasty, a bioengineer at the University of California, San Diego, to reprogram bacteria that could be fed to mice and, in the presence of cancer, would produce a luminescent signal with a simple urine test.
They started with a harmless strain of bacteria called Escherichia coli Nissle 1917, which is commonly added to yogurt and other foods as a probiotic to promote digestive health. First, they fed the bacteria to mice and confirmed that the microbes crossed the gut and colonized tumors in the liver. They engineered the bacteria to produce a naturally occurring enzyme called LacZ when they encountered a tumor. Next, the researchers injected mice with compounds that were precursors for light emitters. These were two-part molecules made up of a sugar linked to luciferin, a luminescent molecule. When bound together, the pair doesn’t emit light, but LacZ acts like a pair of scissors that cuts the two apart. So, in mice that had liver cancer populated by E. coli, the LacZ produced by the microbes released the luminescent compound, which was then excreted in the animals’ urine, turning those samples from yellow to red. What’s more, Bhatia and her colleagues report in the current issue of Science Translational Medicine this week, while conventional imaging techniques struggle to detect liver tumors smaller than 1 square centimeter, this approach was able to flag tumors as small as 1 square millimeter.
In a separate study also reported in the current issue of Science Translational Medicine, researchers led by structural biochemist Jerome Bonnet of the University of Montpellier in France followed a related strategy to detect a key sign of diabetes, namely elevated glucose in the urine of human patients. The researchers added genetic circuitry to the bacteria so that they produced a large amount of a red fluorescent protein once the concentration of glucose in their surroundings reached a certain level. In this case, however, the team’s strain of E. coli wasn’t injected into people first, rather simply added to urine samples, where they produced a color change. For now, this approach isn’t any better than a standard glucose meter. But because the detection scheme can be repurposed to detect other targets, it could serve as a platform for a broad array of future diagnostics.
“They are both nice advances for the field,” says Jim Collins, a synthetic biologist at MIT. But he cautions that both approaches remain years away from being approved for clinical use. Tim Lu, also a synthetic biologist at MIT, agrees. “Taken together this pair of papers demonstrates that synthetic biology will be useful not only for therapeutics but diagnostics as well.” That might just give bacteria a good reputation after all.