New research finds that triclosan, a popular antibacterial chemical, could have the opposite effect and make bacteria more rather than less resilient to antibiotic treatment.
Triclosan is an antibacterial compound present in everyday household and personal-care products, such as toothpaste, soap, dishwashing liquid, deodorants, kitchenware, toys, bedding, clothes, and trash bags.
Manufacturers add the chemical to these products because they believe it kills bacteria that could make people unwell. However, new research now suggests that triclosan might have the opposite effect.
Petra Levin, a professor of biology in the department of Arts & Sciences at the Washington University in St. Louis, led the new research.
Prof. Levin and colleagues conducted both in vitro and in vivo experiments, showing that triclosan makes bacteria stronger and more resilient to antibiotic treatment.
Using a mouse model of urinary tract infection (UTI), the new study reveals that triclosan can interfere with a certain type of antibiotic and explains the mechanism by which it does so.
Prof. Levin and her team set out to examine the effect of triclosan in the presence of bactericidal antibiotics — that is, antibiotics that kill bacteria rather than just halting their growth.
The researchers treated Escherichia coli (E. coli) and MRSA bacteria with these antibiotics in vitro and examined the cells’ behavior. One group of bacterial cells was exposed to triclosan beforehand, while the other group was not.
“[T]triclosan increased E. coli and MRSA tolerant to bactericidal antibiotics as much as 10,000 fold in vitro,” the authors report.
“Triclosan increased the number of surviving bacterial cells substantially,” Prof. Levin continues.
“Normally, one in a million cells survive antibiotics, and a functioning immune system can control them. But triclosan was shifting the number of cells,” the researcher explains.
“Instead of only one in a million bacteria surviving, one in 10 organisms survived after 20 hours. Now, the immune system is overwhelmed.”
Using a mouse model of UTI, the researchers added triclosan to the drinking water of the rodents to recreate the levels that they would expect to find in people.
Approximately 75 percent of individuals in the United States have triclosan in their urine, says the research team, and 10 percent of them have levels that are high enough to stop E. coli from growing.
Next, the researchers treated all of the mice with the antibiotic ciprofloxacin. Corey Westfall, a postdoctoral researcher in Prof. Levin’s lab and the first author of the study, explains this choice of antibiotic.
“Ciprofloxacin (also known as Cipro) was the most interesting one to us because it is a fluoroquinolone that interferes with DNA replication and is the most common antibiotic used to treat UTIs,” Westfall says.
After the treatment, triclosan mice had much higher urine levels of bacteria, as well as a higher number of bacteria stuck to their bladder when the researchers compared them with rodents that had not drunk triclosan.
“The magnitude of the difference in bacterial load between the mice that drank triclosan-spiked water and those that didn’t is striking,” Prof. Levin comments.
“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 the triclosan was the culprit,” she continues.
“We found 100 times more bacteria in the urine of triclosan-treated mice — that is a lot.”
Finally, the researchers wanted to investigate the mechanisms that mediate triclosan effects.
They found that triclosan “collaborates” with a small molecule called ppGpp, which inhibits the growth of cells. PpGpp blocks the biosynthetic pathways that create the building blocks of new cells. Such building blocks are DNA, RNA, proteins, and lipids.
Usually, ppGpp does this when an organism is stressed. In this way, it redirects the organism’s resources from growth towards surviving the stress.
Antibiotics such as Cipro, however, work by targeting DNA synthesis. But if ppGpp shuts down the DNA biosynthesis pathway, Cipro has a harder time killing bacteria.
To see if triclosan, indeed, activates ppGpp, the researchers engineered an E. coli strain that could not produce ppGpp, and they then compared its effects with a strain of E. coli that could.
PpGpp-free E. coli stopped triclosan from protecting bacterial cells against ciprofloxacin.
Prof. Levin and colleagues conclude: “These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.”
“My hope is that this study will serve as a warning that will help us rethink the importance of antimicrobials in consumer products.”
Prof. Petra Levin