Bacterial pathogen shows alarming resistance to common cleaning products, chemists find

The American Chemical Society Infectious Diseases published the research, led by chemists at Emory University. Demonstrates the surprising level of resistance to cleaning agents of multi-resistant products Pseudomonas aeruginosa — a pathogen of particular concern in hospital settings.

The study also identifies biocides that are highly effective against P. aeruginosaincluding a new compound developed at Emory in collaboration with Villanova University. The researchers describe how these biocides work differently than most disinfectants currently in use.

“We hope our findings can help guide hospitals to reconsider protocols for sanitizing patient rooms and other facilities,” said William Wuest, professor of chemistry at Emory and senior author of the study. “We also hope that our discoveries of a new mechanism of action against these bacterial strains can help in the design of future disinfectant products.”

The study’s first authors are Christian Sanchez (who did the work as a chemistry doctoral student at Emory and, after graduation, joined the faculty at Samford University) and German Vargas-Cuebas, a doctoral candidate in microbiology at Emory.

“Pathogen resistance to cleaning agents is an area that is often overlooked,” says Vargas-Cuebas, “but it is an important area of ​​study, especially with the rise of antibiotic-resistant pathogens around the world.”

Kevin Minbiole, a chemistry professor at Villanova, is a co-senior author on the paper.

Robust disinfectants losing strength

Quaternary ammonium compounds, or QACs, are active ingredients commonly seen in household and hospital cleaning products, including some disinfectant sprays and liquids, antibacterial wipes, and soaps.

“There are a handful of QACs that have been stalwart disinfectants for about 100 years, on the front lines of most homes and hospitals,” says Wuest. “Very little has been done to modify their structures because they have long worked so well against many common bacteria, viruses, molds and fungi and are very simple and cheap to manufacture.”

The Wuest laboratory is a leader in studies of QACs and other disinfecting agents. One issue that Wuest and his colleagues have identified is that some bacterial strains are developing resistance to QACs. This trend can cause serious sanitation problems in hospitals.

A critical priority pathogen

More than 2.8 million antimicrobial-resistant infections occur in the United States every year, leading to more than 35,000 deaths, according to the Centers for Disease Control and Prevention (CDC).

The CDC names multidrug-resistant P. aeruginosa as one of seven infection-causing pathogens that have increased in the United States during the COVID-19 pandemic and remain above pre-pandemic levels.

Worldwide, P. aeruginosa it causes more than 500,000 deaths annually and has been named a critical priority pathogen by the World Health Organization.

P. aeruginosa It is commonly found in the environment, including soil and freshwater. Reservoirs in hospital environments can include drains, faucets, sinks and equipment washers. Although the bacteria generally does not affect healthy people, it can cause infections in individuals with cystic fibrosis and those who are immunocompromised, such as patients with burns, cancer, and many other serious illnesses. Patients with invasive devices such as catheters are also at risk due to the ability to P. aeruginosa to form biofilms on the surfaces of these devices.

P. aeruginosalike other gram-negative bacteria, it is enclosed in a second fatty outer membrane that acts as a protective capsule, making it more difficult to kill.

How QACs Kill

QACs have a nitrogen atom at the center of four carbon chains. In simpler terms, the positively charged head of the nitrogen center is attracted to the negatively charged phosphates of the surrounding fatty acids. P. aeruginosa and many other bacteria and viruses. The carbon chain heads act like spearheads, penetrating both protective fatty membranes and internal cell membranes and causing pathogens to disintegrate.

The researchers tested 20 different strains of P. aeruginosa collected in hospitals around the world by Walter Reed National Military Medical Center as part of the Multidrug-Resistant Organism Repository and Surveillance Network.

The results showed that all 20 strains were at least partially resistant to QACs – the common active ingredient in most top-tier cleaning agents – and 80% of the strains were fully resistant to QACs.

“This mechanism has worked for 100 years, essentially cutting through a pathogen’s outer and inner membranes and destroying them,” says Wuest. “We were surprised to see the level to which this appears to no longer be the case.”

Inappropriate use of cleaning agents may be a factor leading to resistance, Wuest theorizes.

“QACs don’t kill immediately,” he explains. “After application, it is important to wait four or five minutes before wiping off these cleaning agents. It is also important to use the correct concentration. If used inappropriately, some bacteria can survive, which can lead to them developing resistance.”

The increased use of cleaning agents during the COVID-19 pandemic may have given P. aeruginosa and some other hard-to-kill pathogens offer more opportunities to develop resistance, he adds.

A new method that ‘works surprisingly well’

For the current paper, the researchers also tested the resistance of the panel of multidrug-resistant drugs. P. aeruginosa strains against a new quaternary phosphonium compound, or QPC, developed in the Wuest and Minbiole laboratories. The results showed that the compound was highly effective in killing all 20 resistant P. aeruginosa strains.

“It works surprisingly well even at low concentrations,” says Vargas-Cuebas.

The researchers demonstrated that their new QPC works by not piercing the protective outer capsule of a P. aeruginosa bacteria, but diffusing through this outer membrane and selectively attacking the inner cell membrane.

“It’s counterintuitive,” notes Wuest. “You would think that the conventional biocide approach of removing both membranes would be a more effective way to kill P. aeruginosa. Why does passive diffusion across the outer membrane and focusing on attacking the inner membrane make our QPC compound more effective? We still don’t know. It’s like a magic trick.”

They showed that this same mechanism underlies the effectiveness of two commercial antiseptics: octenidine, most commonly used in Europe as a hospital antiseptic, and chlorhexidine, a common ingredient in mouthwash.

Wuest and colleagues plan to continue research into how this newly identified mechanism might work against a range of pathogens and how this might translate into new biocides and more effective cleaning protocols in hospitals and other settings.

“Our work is paving the way for much-needed innovations in disinfectant research,” says Wuest.

Additional authors on the paper include Emory graduate student Marina Michaud, Emory graduate student Shehreen Siddiqui, and Emory PhD graduates Ryan Allen and Kelly Morrison-Lewis.

The work was funded by the National Institutes of Health.