For centuries, silver has been used as an antibacterial agent to kill harmful bacteria. Ancient civilizations applied metals to open wounds. The captain threw the silver coins into the bucket to keep the drinking water fresh.

In today's hospitals, nanosilver is used in bandages to treat burn patients, to eliminate pathogenic microorganisms on the catheter, and to fight the "superbug" that is already resistant to traditional antibiotics. However, the molecular mechanism of nanosilver, including silver ions, and the resistance of these microorganisms to silver are not fully understood. Now, a new study led by biologists at the University of Calgary Science helps to enhance the understanding of the antibacterial properties of silver.

The team conducted a chemical genetic screening of the "libraries" of 4,000 bacterial E. coli mutants in which the unique genes in each strain have been "knocked out" or deleted.

The team identified genes in all of these strains that showed resistance or sensitivity when exposed to silver, producing the first genetic map of genes that cause silver resistance or toxicity in E. coli.

"Our study is the first to evaluate genetic responses in cells that allow growth in the presence of silver, providing a list of resistant and toxic genes and mapping them to biological processes," Dr. Raymond Turner said. , Ph.D., Professor of Biochemistry, Department of Biological Sciences.

Research identifies new genes and molecular mechanisms involved in silver toxicity

Dr. Turner's Ph.D. student Natalie Gugala has mapped all 225 genes that are resistant or sensitive to their corresponding biological pathways. These cellular mechanisms include transporting metals through the cell wall, generating energy, regulating cells and other processes.

"We have shown that there are many different genes that can be affected and there are several different ways," said Gujara, the first author of the team's scientific paper.

“Silver is likely to work with bacteria in a variety of ways,” said Dr. Gordon Chua, associate professor of integrated cell biology at the Department of Biological Sciences. “Our research identified new genes and molecular mechanisms involved in silver toxicity and resistance.”

The team's paper "Using Chemical Genetic Screens to Enhance Our Understanding of the Antibacterial Properties of Silver" was published in the journal Genes.

The important role of molecules in our health

E. coli is just one of many microorganisms that can cause disease and life-threatening infections. Many bacteria and other microorganisms are increasingly resistant to traditional antibiotics.

The team's research is well suited to the big challenges of the science school. Specifically, “personalized health at the molecular level” prioritizes research aimed at minimizing antibiotic resistance and understanding the role of molecules in our health.

Turner said: "If we want to continue to use silver and develop more silver-based antibacterial agents, we need to understand how silver works."

Together with antibiotics: custom designed metal antimicrobials

Determining how silver and other metals (such as copper and gallium) can kill bacteria at the molecular level can improve medical therapy. Turner pointed out that some studies have shown that adding a metal that no longer works to traditional antibiotics will make the drug effective again. “I foresee that we will use custom-designed metal antibacterials and antibiotics.

"This personalized approach to health, using a study like ours, identifies a set of marker genes that can be used to select specific metal antibacterial therapies to combat bacterial infections in individual patients," he added.

The popularity of silver as a bacterial killer has led the company to embed tiny nano-silver particles in running shirts, underwear, socks, insoles, food cutting boards, toothbrushes and a range of other "antibacterial" consumer products.

But what is worrying is that these growing non-medical applications may cause some bacterial strains to be resistant to silver and other antimicrobial metals - just as some bacteria do with traditional antibiotics. “We need to make sure we use these metals in the right environment,” Gujara said. “If we know how they work, we may be better able to prevent them from being used improperly.”

Robot helps screen bacteria

The team used robots for chemical genetic screening, which was designed for automated processing and processing of high-density bacterial colonies in Chua Laboratories.

The researchers then used the "colony score" software to measure the difference in growth and size of each bacterial colony. E. coli strains with deletion genes are involved in sensitivity or toxicity to silver, resulting in larger colonies. Strains with genes associated with resistance grow smaller colonies.

Compared to most previous studies, the team used a new type of chronic non-fatal exposure method that exposed bacteria to an acute lethal dose of silver for toxicity only.

Kate Chatfield-Reed, then a Ph.D. student at Chua, helped "standardize" or standardize data to identify strains that showed statistically significant changes in growth rate when exposed to silver compared to untreated control panels.

Source: Physorg