Categories: world

Triclosan added to consumer products affects the response to antibiotic treatment

E. coli from the strain used in this study. The cell wall is shown in red and DNA is shown in blue. Credit: Petra Levin Laboratory, Washington University in St. LouisThe food gangs are betrayed with products that promise to kill bacteria. People snap up the objects to protect themselves from the bacteria that make them sick. New research from Washington University in St. Louis finds, however, that a chemical that will kill bacteria actually makes them stronger and more capable of surviving antibiotic treatment. The study, available online February 1 9 in the journal Antimicrobials and Chemotherapy suggests that exposure of triclosan can inadvertently drive bacteria into a state where they can tolerate normally lethal concentrations of antibiotics including those antibiotics commonly used to treat urinary tract infections (UTIs). Triclosan is the active ingredient responsible for the antibacterial property marketed on many consumer products. It is added to toothpaste, mouthwash, cosmetics and even clothes, baby toys and credit cards with the intention of reducing or preventing bacterial growth. "To effectively kill bacterial cells, triclosan is added to products at high concentrations," said Petra Levin, a professor of biology in the arts and sciences. In 2017, the US Food and Drug Administration quoted both safety issues and lack of efficiency when it was recommended to add triclosan to consumer soaps, but these guidelines did not deter companies from adding it to other products. In addition, Levin says: "Triclosan is very stable. It is long in the body and in the…



E. coli from the strain used in this study. The cell wall is shown in red and DNA is shown in blue. Credit: Petra Levin Laboratory, Washington University in St. Louis

The food gangs are betrayed with products that promise to kill bacteria. People snap up the objects to protect themselves from the bacteria that make them sick. New research from Washington University in St. Louis finds, however, that a chemical that will kill bacteria actually makes them stronger and more capable of surviving antibiotic treatment.

The study, available online February 1

9 in the journal Antimicrobials and Chemotherapy suggests that exposure of triclosan can inadvertently drive bacteria into a state where they can tolerate normally lethal concentrations of antibiotics including those antibiotics commonly used to treat urinary tract infections (UTIs).

Triclosan is the active ingredient responsible for the antibacterial property marketed on many consumer products. It is added to toothpaste, mouthwash, cosmetics and even clothes, baby toys and credit cards with the intention of reducing or preventing bacterial growth.

“To effectively kill bacterial cells, triclosan is added to products at high concentrations,” said Petra Levin, a professor of biology in the arts and sciences.

In 2017, the US Food and Drug Administration quoted both safety issues and lack of efficiency when it was recommended to add triclosan to consumer soaps, but these guidelines did not deter companies from adding it to other products. In addition, Levin says: “Triclosan is very stable. It is long in the body and in the environment.”

The new study in mice reveals the extent to which the secretion of triclosan limits the body’s ability to respond to antibiotic treatment for urinary tract infection.

Escaping death

Some antibiotics kill bacterial cells, while others prevent them from growing.

Levin and her colleagues were particularly interested in bactericidal antibiotics that can kill bacterial cells and are usually prescribed by doctors to treat bacterial infections. They wanted to know if triclosan could protect bacteria from death in the presence of killing antibiotics.

Corey Westfall, postdoctoral fellow in the Levin lab, treated bacterial cells with bactericidal antibiotics and tracked their ability to survive over time. In one group, the bacteria were exposed to triclosan before they received the bactericidal antibiotic. In the other group they were not.

“Triclosan increased the number of surviving bacterial cells substantially,” Levin says. “Normally one in a million cells survives antibiotics and a functioning immune system can control them. But triclosan changed the number of cells. Instead of only one million bacteria surviving, one in 10 survived after 20 hours. Now, the immune system is overwhelmed.” Triclosan exposure allowed the bacteria to escape the death of antibiotics. And the protective property was not limited to a single family of antibiotics. In fact, several antibiotics considered unique in how they kill cells were less effective in killing bacteria exposed to triclosan.

“Triclosan increased tolerance to a wide variety of antibiotics,” said Westfall. “Ciprofloxacin (also known as Cipro) was the most interesting to us because it is a fluoroquinolone that interferes with DNA replication and is the most common antibiotic used to treat UTI.”

Antibiotics cannot do their job with triclosan around

UTI occurs when bacteria, primarily Escherichia coli (E. coli), enter and infect the urinary tract. Antibiotics such as Cipro are commonly used to kill the bacteria and treat the infection.

UTIs are common; so is the exposure to triclosan. A Shocking Share – About 75 percent of adults in the United States have detectable levels of triclosan in the urine. About 10 percent of adults have levels high enough to prevent E. coli from growing. Could triclosan’s presence in the body interfere with the treatment of UTI?

Westfall and Levin worked with co-workers at Washington University School of Medicine in St. Louis to answer this question.

Ana Flores-Mireles, an assistant professor at the University of Notre Dame, worked on this study as a postdoctoral researcher in the lab by Scott Hultgren, Helen L. Stoever professor of molecular microbiology at the medical school. With the help of Jeffrey Henderson, a professor of medicine and molecular biology, she found that mice who drink triclosan-spiked water have urinary tract levels similar to those reported in humans.

“This result meant that we could actually test the effect that human urine levels of triclosan have during the antibiotic treatment of UTI in mice,” Levin says.

All mice with the infection received Cipro to treat UTI. Only some of the mice drank triclosan-nailed water. After antibiotic treatment, mice with triclosan exposure had a large number of bacteria in the urine and stuck in the bladder; mice without exposure had significantly lower bacterial counts.

“The size of the difference in bacterial load between the mice who drank triclosan-nailed water and those who did not beat,” says Levin.

“If the difference in the number of bacteria between the groups was less than tenfold, it would be difficult to make a strong case that triclosan was the culprit,” Levin added. “We found 100 times more bacteria in the urine of triclosan-treated mice – that’s a lot.”

This striking result has an equally striking message. Antibiotics are less effective in treating UTI when triclosan is around, at least in mice

Triclosan’s dirty arms: ppGpp

Triclosan interferes with the disruption of antibiotics, but how?

Levin and her colleagues found that triclosan works with a cell growth inhibitor, a small molecule called ppGpp, to make the cells less sensitive to antibiotics.

During stress periods, ppGpp responds by shutting down the biosynthetic pathways that make the building blocks DNA, RNA, protein and fat – which ultimately become new cells. This response helps to divert resources from growth and survival.

“There is a rule in medicine that you don’t give drugs that slow down cell growth before drugs that kill cells,” Levin says.

Bactericidal antibiotics kill off targeting specific biosynthetic pathways. Ampicillin targets the enzymes that make the bacterial cell wall, for example while Cipro targets DNA synthesis. When these paths are shut down, germicidal antibiotics have problems doing their job.

If triclosan triggers ppGpp, biosynthesis is limited and bactericidal antibiotics become ineffective in killing cells. Biosynthesis continues in bacteria lacking ppGpp, but these cells are expected to die.

Levin and colleagues tested their hypothesis by constructing E. coli mutants that could not do ppGpp and compared them to E. coli that could do ppGpp. The absence of ppGpp in mutant E. coli removed the ability of triclosan to protect the cells from bactericidal antibiotics.

Although clinical trials would definitely have to prove that triclosan interferes with anti-antibiotic drugs in humans, Levin said: “My hope is that this study will act as a warning to help us rethink the importance of antimicrobials in consumer products.”


Explore further:
Minnesota prohibits antibacterial chemical triclosan in soap

More information:
Corey Westfall et al. The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and decreases antibiotic treatment up to 100 times in vivo, antimicrobial agents and chemotherapy (2019). DOI: 10.1128 / AAC.02312-18

Journal reference:
Antimicrobial agents and chemotherapy

Provided by:
Washington University in St. Louis

Share
Published by
Faela