Researchers find one-two punch may help fight against Salmonella

May 14, 2020

Hamilton, ON (May 14, 2020) - McMaster University researchers have discovered a combination punch to treat drug-resistant infections that is showing promise based on testing in mice.

Researchers found that a natural product called dephostatin is an effective partner for the antibiotic colistin in treating infections caused by the bacteria Salmonella.

Colistin is considered a last-resort antibiotic for multidrug-resistant bacterial infections due its toxic effect on the body, which has limited its use in medicine. However, when paired together, dephostatin allowed for drastically lower concentrations of colistin in a treatment regimen for Salmonella infection in mice that maintained the antibiotic's effectiveness.

The study details are published in Cell Chemical Biology.

"The rise of antibiotic resistance has ushered in the post-antibiotic age, and alternatives to antibiotics are urgently required," said Caressa Tsai, first author of the study and a PhD student in biochemistry and biomedical sciences in the Coombes lab at McMaster. "Solving the antibiotic resistance crisis will require us to shift away from the traditional view of antibiotic discovery."

The World Health Organization has classified antibiotic-resistant Salmonella, which can cause infection from eating contaminated foods, as a high-priority pathogen.

In their study, researchers found that dephostatin does not kill Salmonella or stop it from growing. Instead, dephostatin prevents Salmonella from causing infection in two ways: It blocks its ability to resist being killed by immune cells and it enhances its sensitivity to colistin.

While the initial findings were done using a method of experimentation called high-throughput screening, the researchers were excited to find that co-administering dephostatin and colistin in mice with a lethal Salmonella infection significantly prolonged animal survival and used a lower concentration of colistin than is normally required for treatment, thereby reducing its toxic effect.

By the numbers, treatment with colistin alone extended survival of almost 88 per cent of mice to approximately five days post infection and 25 per cent of mice survived to the end of the experiment. However, more than 62 per cent of mice treated with both dephostatin and colistin survived the infection, indicating a significant improvement over therapy with one antibiotic.

"Traditional antibiotics all work in a similar way - they clear infections by killing bacteria," said Tsai. "Here, we were interested in a different approach - keeping bacteria alive, but chemically inactivating important pathways to prevent them from causing infection."

Researchers are continuing their research to understand how dephostatin works against Salmonella. Their ongoing work will explore the activity of dephostatin alone and in combination therapies during the treatment of infected animals.

"Dephostatin appears to knock out two important regulatory pathways that control Salmonella virulence and antibiotic resistance mechanisms," said Coombes, corresponding author and a professor in the Department of Biochemistry and Biomedical Sciences at McMaster University. He holds the Canada Research Chair in Infectious Disease Pathogenesis.

"This research highlights the opportunities in taking a different approach than traditional antibiotic discovery and is enabling new drug combinations to emerge."
The study is funded by the Canadian Institutes of Health Research and the Boris Family Fund for Health Research Excellence.


Photos attached of Caressa Tsai and Brian Coombes.

Photo captions:

Caressa Tsai is a PhD student in biochemistry and biomedical sciences at McMaster University. Photo courtesy McMaster University

Brian Coombes is a professor in the Department of Biochemistry and Biomedical Sciences at McMaster University and the Canada Research Chair in Infectious Disease Pathogenesis. Photo courtesy McMaster University

For more information:

Veronica McGuire
Media Relations
McMaster University
905-525-9140, ext. 22169

McMaster University

Related Salmonella Articles from Brightsurf:

Sneaky salmonella finds a backdoor into plants
Researchers have discovered that bacteria such as salmonella, E.coli and listeria have a backdoor to take advantage of humans' reliance on leafy greens for a healthy diet.

Re-trafficking proteins to fight Salmonella infections
New study demonstrates how monitoring all cellular proteins over time and space can improve our understanding of host-pathogen interactions.

Researchers find one-two punch may help fight against Salmonella
Researchers found that dephostatin does not kill Salmonella or stop it from growing.

Food scientists slice time off salmonella identification process
Researchers from Cornell University, the Mars Global Food Safety Center in Beijing, and the University of Georgia have developed a method for completing whole-genome sequencing to determine salmonella serotypes in just two hours and the whole identification process within eight hours.

The discovery of ancient Salmonella
Oldest reconstructed bacterial genomes link agriculture and herding with emergence of new disease.

The function of new microRNAs are identified in Salmonella and Shigella infections
The research, published in Nature Microbiology, could help the search for more effective medicine and delves deeper into understanding the role of microRNAs in gene expression.

Salmonella the most common cause of foodborne outbreaks in the European Union
Nearly one in three foodborne outbreaks in the EU in 2018 were caused by Salmonella.

The nature of salmonella is changing -- and it's meaner
Salmonella is acting up in Michigan, and it could be a model for what's happening in other states, according to a new Michigan State University study.

Salmonella -- how the body fights back
New research shows how our immune system fights back against Salmonella infection.

For salmonella detection, genomic tool emerges as a key
The world's food supply will become safer as the food industry shifts to high-resolution, whole-genome sequencing -- which examines the full DNA of a given organism all at once.

Read More: Salmonella News and Salmonella Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to