Ultrasound to Command Bacteria to Nuke Tumors

Scientists at Caltech have genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.

The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.

The starting point for their work was a strain of E. coli called Nissle 1917, which is approved for medical uses in humans. After being injected into the bloodstream, these bacteria spread throughout the body. The patient’s immune system then destroys them—except for those bacteria that have colonized cancerous tumors, which offer an immunosuppressed environment.

To turn the bacteria into a useful tool for treating cancer, the team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allow the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.

By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42–43 degrees Celsius. Since normal human body temperature is 37 degrees Celsius, these strains do not begin producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until an outside source heats them to their trigger temperature.

But how do you heat bacteria that are located in one specific location, potentially deep inside the body where a tumor is growing? For this, the team used focused ultrasound (FUS). FUS is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb, but has higher intensity and is focused into a tight point. Focusing the ultrasound on one spot causes the tissue in that location to heat up, but not the tissue surrounding it; by controlling the intensity of the ultrasound, the researchers were able to raise the temperature of that tissue to a specific degree.

Source: https://www.caltech.edu/

How To Kill Antibiotic-Resistant SuperBugs

A new compound which visualises and kills antibiotic-resistant superbugs has been discovered by scientists at the University of Sheffield and Rutherford Appleton Laboratory (RAL). The team, led by Professor Jim Thomas, from the University of Sheffield’s Department of Chemistry, is testing new compounds developed by his PhD student Kirsty Smitten on antibiotic resistant gram-negative bacteria, including pathogenic E. coli.

Gram-negative bacteria strains can cause infections including pneumonia, urinary tract infections and bloodstream infections. They are difficult to treat as the cell wall of the bacteria prevents drugs from getting into the microbeAntimicrobial resistance is already responsible for 25,000 deaths in the EU each year, and unless this rapidly emerging threat is addressed, it’s estimated by 2050 more than 10 million people could die every year due to antibiotic resistant infections. Doctors have not had a new treatment for gram-negative bacteria in the last 50 years, and no potential drugs have entered clinical trials since 2010.

The new drug compound has a range of exciting opportunities. As Professor Jim Thomas explains: “As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL.

Gram negative bacteria. Credit: University of Sheffield

“As the compound is luminescent it glows when exposed to light. This means the uptake and effect on bacteria can be followed by the advanced microscope techniques available at RAL“, explains Professor Jim Thomas. This breakthrough could lead to vital new treatments to life-threatening superbugs and the growing risk posed by antimicrobial resistance.”

The studies at Sheffield and RAL have shown the compound seems to have several modes of action, making it more difficult for resistance to emerge in the bacteria. The next step of the research will be to test it against other multi-resistant bacteria.

Source: https://www.sheffield.ac.uk/

How To Kill Deadly Hospital Bacteria

Scientists at Aston University (UK) have discovered a technique similar to medieval stained glass-making that can completely eradicate the deadliest hospital infections within hours.

Using a so-called bioactive phosphate glass containing small amounts of the metallic element cobalt, the researchers were able to achieve a “complete kill” of the deadly bacterial infections E.coli and Candida albicans (a fungal infection associated with surgery), as well as a near-complete kill of Staphylococcus aureus (the drug-resistant form of which is MRSA).

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Lead researcher, Dr Richard Martin of Aston University in Birmingham, said the findings had significant implications, offering the possibility of cheap, antimicrobial implants and coatings to combat the most common sources of infections associated with medical care. Avoiding the need for antibiotics, it is also thought the bioactive glass could be effective against drug-resistantsuperbugs’, helping to tackle the growing problem of antimicrobial resistance (AMR).

According to the European Centre for Disease Prevention and Control (ECDC), over four million people in Europe get a healthcare-associated infection (HAI) every year, and around 37,000 die as a direct result of the infection. In its most recent survey of hospital patients, Public Health England found that 6.4% had a healthcare-associated infection.

In the study, published in the journal ACS Biomaterials, the researchers used a centuries-old technique to make glass laced with trace amounts of cobalt in a furnace heated to over 1,000°C, before rapid cooling to prevent crystallisation. These were then ground down into a fine powder and put into contact with bacteria in petri dishes. The glasses contained varying concentrations of cobalt, providing a controlled release of antimicrobial ions as they dissolved. At the highest concentration, the glass completely eradicated E.coli within just six hours, with a “complete kill” also observed for C.albicans within 24 hours. S.aureus levels were reduced by 99% after 24 hours.

Source: https://www2.aston.ac.uk/