Ultrashort-pulse lasers kill bacterial superbugs, spores

Life-threatening bacteria are becoming ever more resistant to antibiotics, making the search for alternatives to antibiotics an increasingly urgent challenge. For certain applications, one alternative may be a special type of laser.

Researchers at Washington University School of Medicine in St. Louis have found that lasers that emit ultrashort pulses of light can kill multidrug-resistant bacteria and hardy bacterial spores. The findings, available online in the Journal of Biophotonics, open up the possibility of using such lasers to destroy bacteria that are hard to kill by other means. The researchers previously have shown that such lasers don't damage human cells, making it possible to envision using the lasers to sterilize wounds or disinfect blood products.

"The ultrashort-pulse laser technology uniquely inactivates pathogens while preserving human proteins and cells," said first author Shaw-Wei (David) Tsen, MD, PhD, an instructor of radiology at Washington University's Mallinckrodt Institute of Radiology (MIR). "Imagine if, prior to closing a surgical wound, we could scan a laser beam across the site and further reduce the chances of infection. I can see this technology being used soon to disinfect biological products in vitro, and even to treat bloodstream infections in the future by putting patients on dialysis and passing the blood through a laser treatment device."

Tsen and senior author Samuel Achilefu, PhD, the Michel M. Ter-Pogossian Professor of Radiology and director of MIR's Biophotonics Research Center, have been exploring the germicidal properties of ultrashort-pulse lasers for years. They have shown that such lasers can inactivate viruses and ordinary bacteria without harming human cells. In the new study, conducted in collaboration with Shelley Haydel, PhD, a professor of microbiology at Arizona State University, they extended their exploration to antibiotic-resistant bacteria and bacterial spores.

The researchers trained their lasers on multidrug-resistant Staphylococcus aureus (MRSA), which causes infections of the skin, lungs and other organs, and extended spectrum beta-lactamase-producing Escherichia coli (E. coli), which cause urinary tract infections, diarrhea and wound infections. Apart from their shared ability to make people miserable, MRSA and E. coli are very different types of bacteria, representing two distant branches of the bacterial kingdom. The researchers also looked at spores of the bacterium Bacillus cereus, which causes food poisoning and food spoilage. Bacillus spores can withstand boiling and cooking.

In all cases, the lasers killed more than 99.9% of the target organisms, reducing their numbers by more than 1,000 times.

Viruses and bacteria contain densely packed protein structures that can be excited by an ultrashort-pulse laser. The laser kills by causing these protein structures to vibrate until some of their molecular bonds break. The broken ends quickly reattach to whatever they can find, which in many cases is not what they had been attached to before. The result is a mess of incorrect linkages inside and between proteins, and that mess causes normal protein function in microorganisms to grind to a halt.

"We previously published a paper in which we showed that the laser power matters," Tsen said. "At a certain laser power, we're inactivating viruses. As you increase the power, you start inactivating bacteria. But it takes even higher power than that, and we're talking orders of magnitude, to start killing human cells. So there is a therapeutic window where we can tune the laser parameters such that we can kill pathogens without affecting the human cells."

Heat, radiation and chemicals such as bleach are effective at sterilizing objects, but most are too damaging to be used on people or biological products. By inactivating all kinds of bacteria and viruses without damaging cells, ultrashort-pulse lasers could provide a new approach to making blood products and other biological products safer.

Read more at Science Daily

New insight into bacterial structure to help fight against superbugs

Scientists from the University of Sheffield have produced the first high-resolution images of the structure of the cell wall of bacteria, in a study that could further understanding of antimicrobial resistance.

The research, published in Nature, revealed a new and unexpected structure of the outer bacterial layers of the bacterium Staphylococcus aureus.

The findings set a new framework for understanding how bacteria grow and how antibiotics work, overturning previous theories about the structure of the outer bacterial layers.

The images give unprecedented insight into the composition of the bacterial cell wall and will inform new approaches to developing antibiotics in order to combat antibiotic resistance. There are no other examples of studies of the cell wall in any organism at comparable resolution, down to the molecular scale.

Laia Pasquina Lemonche, a PhD Researcher from the University of Sheffield's Department of Physics and Astronomy, said: "Many antibiotics work by inhibiting the bacteria's production of a cell wall, a strong but permeable skin around the bacteria which is critical for its survival.

"We still don't understand how antibiotics like penicillin kill bacteria, but this isn't surprising because until now we had remarkably little information about the actual organisation of the bacterial cell wall. This study provides that essential stepping stone which we hope will lead to both a better understanding of how antibiotics work and to the future development of new approaches to combat antimicrobial resistance."

The team used an advanced microscopy technique called Atomic Force Microscopy (AFM), which works by using a sharp needle to feel the shape of a surface and build an image similar to a contour map, but at the scale of individual molecules.

Professor Jamie Hobbs, Professor of Physics at the University of Sheffield, said: "It is by physicists and biologists working together that we've been able to make these breakthroughs in our understanding of the bacterial cell wall."

The researchers are now using the same techniques to understand how antibiotics change the architecture of the cell wall and also how changes in the cell wall are important in antimicrobial resistance.

From Science Daily