Vaccine for urinary tract infections comes closer to reality

Washington, Sept 18 (ANI): A simple vaccine may soon be available to protect against urinary tract infections, thanks to researchers from University of Michigan.

The study conducted over mice showed that the vaccine prevented infection and produced key types of immunity.

It alerts the immune system to iron receptors on the surface of Escherichia coli bacteria that perform a critical function allowing infection to spread.

Administered in the nose, it induces an immune response in the body’s mucosa, a first line of defense against invading pathogens. The response, also produced in mucosal tissue in the urinary tract, should help the body fight infection where it starts.

The researchers used novel systematic approach, combining bioinformatics, genomics and proteomics, to look for key parts of the bacterium that could be used in a vaccine to elicit an effective immune response.

The team, led by Dr. Harry L.T. Mobley, screened 5,379 possible bacterial proteins and identified three strong candidates to use in a vaccine to prime the body to fight E. coli.

Mobley’s team is currently testing more strains of E. coli obtained from women treated at U-M.

If the robust immunity achieved in mice can be reproduced in humans, it could be the first ever vaccine for urinary tract infections.

Most of the strains produce the same iron-related proteins that can be vaccine targets, an encouraging sign that the vaccine could work against many urinary tract infections.

The findings are published in the open-access journal PLoS Pathogens. (ANI)

Scientists uncover vulnerable enzyme that can be targeted to kill dangerous pathogens

Washington, August 28 (ANI): A collaborative study conducted by researchers from three institutions in the U.S. has shown that an enzyme, which is essential to many bacteria, can be targeted to kill dangerous pathogens.

Experts at Burnham Institute for Medical Research (Burnham), University of Texas Southwestern Medical Center and University of Maryland have also identified chemical compounds that can inhibit this enzyme, and suppress the growth of pathogenic bacteria.

Writing about their study in the journal Chemistry and Biology, the researchers say that their findings are essential to develop new broad-spectrum antibacterial agents to overcome multi-drug resistance.

Dr. Andrei Osterman, an associate professor in Burnham’s ioinformatics and Systems Biology program, targeted the acterial nicotinate mononucleotide adenylyltransferase (NadD), an essential enzyme for nicotinamide adenine dinculeotide (NAD) biosynthesis, which has many crucial functions in nearly all important pathogens.

The bacterial NadD differs significantly from the human enzyme.

“It’s clear that because of bacterial resistance, we need new, wide-spectrum antibiotics. This enzyme is indispensable in many pathogens, so finding ways to inhibit it could give us new options against infection,” said Dr. Osterman.

The research team used a structure-based approach to search for low-molecular-weight compounds that would selectively inhibit bacterial NadD, but not the human equivalent, by screening, in silico, more than a million compounds.

In their experiments, they tested the best predicted compounds against Escherichia coli and Bacillus anthracis (anthrax), which led them to a handful of versatile inhibitory chemotypes, which they explored in detail.

Using protein crystallography, a 3D structure of the enzyme in complex with one of the inhibitors was solved providing guidelines for further drug improvement.

“This is proof-of-concept that NadD is a good target to create antibacterial agents. This knowledge will be useful for both biodefense and public health. The next step is to find better inhibitors. We do not have a silver bullet yet, but we are certainly hitting a golden target,” said Dr Osterman.

The research was supported by a grant from the National Institute of Allergy and Infectious Diseases. (ANI)

Light-activated antibacterial coating may help fight hospital-acquired infections

Washington, Mar 31 (ANI): Scientists at the UCL Eastman Dental Institute have developed a new tool to combat hospital-acquired infections- antibacterial coating that is activated by light.

The research team, led by Zoie Aiken, have tested the new coating with antibacterial properties, and found that it could kill 99.9 percent of Escherichia coli bacteria when a white hospital light was shone on its surface to activate it.

Made of titanium dioxide with added nitrogen, the veneer-like surface, when activated by white light-similar to those used in hospital wards and operating theatres-produced a decrease in the number of bacteria surviving on the test surface.

The hospital environment is usually full of microbes responsible for healthcare-associated infections (HCAI).

Thus, there’s a need for new ways to prevent the spread of these pathogens to patients.

And it is possible to apply antibacterial coatings to frequently touched hospital surfaces to kill any bacteria present and help reduce the number of HCAI.

Titanium dioxide based coatings can kill bacteria after activation with UV light.

And the addition of nitrogen to these coatings enables photons available in visible light to be utilised to activate the surface and kill bacteria.

Aiken said: “The activity of the coating will be assessed against a range of different bacteria such as MRSA and other organisms which are known to cause infections in hospitals. At present we only know that the coating is active against Escherichia coli. However, E. coli is more difficult to kill than bacteria from the Staphylococcus group which includes MRSA, so the results to date are encouraging.

“The coating has currently been applied onto glass using a method called APCVD (atmospheric pressure chemical vapour deposition.

“We are also experimenting with different materials such as plastic. As an example, the coating could be applied to a plastic sheet that could be used to cover a computer keyboard on a hospital ward. The lights in the ward will keep the coating activated, which will in turn continue to kill any bacteria that may be transferred onto the keyboard from the hands of healthcare workers.”

The study was presented at the Society for General Microbiology meeting in Harrogate. (ANI)

How cranberry helps prevent urinary tract infections

Washington, Mar 10 (ANI): Chemicals present in cranberries prevent infection-causing bacteria from attaching to the cells that line the urinary tract, says a new study.

According to a report published in Journal of Medicinal Food, chemicals found in cranberry products called proanthocyanidins (PACs) prevent E. coli from adhering to these urinary tract epithelial cells by affecting the surface properties of the bacteria.

To reach the conclusion, Paola Pinzsn-Arango, Yatao Liu, and Terri Camesano, from Worcester Polytechnic Institute, in Massachusetts, exposed E. coli grown in culture to either light cranberry juice cocktail or cranberry PACs and measured the adhesion forces between the bacteria and a silicon surface using atomic force microscopy.

They demonstrated that the longer the bacteria were exposed to either the cranberry juice or the PACS the greater the decrease in bacterial attachment. In the article entitled, “Role of Cranberry on Bacterial Adhesion Forces and Implications for Escherichia coli-Uroepithelial Cell Attachment,” the authors also concluded that this effect was reversible, and that bacteria regrown in an environment without cranberry juice or PACS regained the ability to attach to the model surface.

“Cranberries, one of only three species of fruits native to North America, has a long history of medicinal food use. Native Americans used the fruit for the treatment of bladder and kidney ailments hundreds of years ago. The article by Camesano and co-workers is a milestone in the understanding of its mechanism of action,” says Sheldon S. Hendler, PhD, MD, Co-Editor-in-Chief of the Journal, and Clinical Professor of Medicine, University of California, San Diego. (ANI)

Engineered viruses may help fight drug-resistant superbugs

London, Mar 3 (ANI): A virus that weakens bacterial defence systems is the latest weapon in the fight against drug-resistant superbugs.

Researchers in the United States have engineered viruses to weaken the bacteria, leaving the bugs more vulnerable to antibiotics, reports Nature.

The ‘bacteriophages’ or just ‘phages’ were programmed to target a DNA repair system that allows the bacteria to survive antibiotics.

Used alongside the drugs, the viruses wipe out bacterial defences and prevent resistance from developing.
With more bacteria becoming resistant to the most commonly used antibiotics, the viral approach could extend the useful lifetime of these drugs.

Bioengineer James Collins of Boston University in Massachusetts and his then graduate student, Timothy Lu, genetically engineered a phage called M13, which does not cause infected cells to explode, to produce a bacterial protein called lexA3 – which impairs a bacterium’s ability to repair damaged DNA.

When the modified M13 phage infects a bacterium, in this case Escherichia coli, it produces lexA3, which renders the bacterium more vulnerable to DNA-damaging drugs.

The researchers found that the phage increased the ability of the antibiotic ofloxacin to kill E. coli grown in culture, even when the bacteria were resistant to the antibiotic on its own.

The findings suggest that this type of phage therapy could rejuvenate antibiotics that have been deemed no longer effective.

The results of the study conducted on mice were also promising.

80 percent of animals that received both ofloxacin and the modified M13 phage survived infection with a disease-causing strain of E. coli, compared with only a 20 percent survival rate among infected mice treated with the antibiotic alone. (ANI)