A recent study has uncovered that a prominent bacterial pathogen shows significant resistance to the active ingredients in cleaning products typically used in hospitals and homes.
A recent study has uncovered that a prominent bacterial pathogen shows significant resistance to the active ingredients in cleaning products typically used in hospitals and homes.
This research, published by the American Chemical Society Infectious Diseases, was led by chemists from Emory University. It highlights the unexpected extent of resistance exhibited by multidrug-resistant Pseudomonas aeruginosa, a pathogen that poses significant risks in healthcare environments.
The study also pinpoints biocides that are notably effective against P. aeruginosa, including a new compound developed through collaboration between Emory University and Villanova University. The researchers explain that these biocides operate differently from most disinfectants currently available.
“We aim for our findings to assist hospitals in reevaluating their cleaning protocols for patient rooms and other areas,” states William Wuest, a professor of chemistry at Emory and a senior author of the study. “We also hope that our discovery of a new mechanism to combat these bacterial strains will aid in the development of future disinfectant products.”
The lead authors of this research include Christian Sanchez (formerly an Emory PhD student in chemistry, now on the faculty at Samford University) and German Vargas-Cuebas, a PhD candidate in microbiology at Emory.
“The issue of pathogens becoming resistant to cleaning agents is often neglected,” comments Vargas-Cuebas. “However, this is a critical area of research, especially given the global increase in antibiotic-resistant pathogens.”
Kevin Minbiole, a chemistry professor at Villanova, is a co-senior author of the paper.
Traditional disinfectants becoming less effective
Quaternary ammonium compounds (QACs) are widely used active ingredients in various cleaning products found in homes and hospitals, such as disinfectant sprays, antibacterial wipes, and soaps.
“A small selection of QACs has served as primary disinfectants for nearly a century, standing as the first line of defense in many homes and healthcare facilities,” Wuest explains. “These compounds have not undergone significant modifications because they have historically been effective against a broad range of bacteria, viruses, molds, and fungi, and they are easy and inexpensive to produce.”
The Wuest lab is at the forefront of research related to QACs and other disinfectants. They have identified a growing issue where certain bacterial strains are becoming resistant to QACs, which poses a serious risk for sanitation in hospitals.
A high-priority pathogen
According to the Centers for Disease Control and Prevention (CDC), there are more than 2.8 million antimicrobial-resistant infections annually in the United States, resulting in over 35,000 fatalities.
The CDC has categorized multidrug-resistant P. aeruginosa as one of seven pathogens responsible for infections that increased during the COVID-19 pandemic and which continue to be at elevated levels.
Globally, P. aeruginosa accounts for over 500,000 deaths each year and has been designated as a pathogen of significant concern by the World Health Organization.
This bacterium is commonly present in the environment, notably in soil and freshwater. In healthcare settings, it can thrive in drains, taps, sinks, and equipment washers. Although it typically does not harm healthy individuals, it can lead to infections in people with cystic fibrosis and those with weakened immune systems, including patients with burns, cancer, and various severe conditions. Individuals with invasive devices like catheters are also at risk due to P. aeruginosa‘s ability to form biofilms on these devices.
Like many gram-negative bacteria, P. aeruginosa is safeguarded by a fatty outer membrane that complicates efforts to eliminate it.
Mechanism of QACs
QACs feature a nitrogen atom surrounded by four carbon chains. Simply put, the positively charged nitrogen attracts the negatively charged phosphates of the fatty acids enveloping P. aeruginosa and other bacteria and viruses. The tips of the carbon chains act like sharp points, puncturing both the outer fatty membranes and inner cellular membranes, ultimately leading to the pathogen’s destruction.
The researchers examined 20 different drug-resistant P. aeruginosa strains collected from hospitals worldwide, facilitated by the Walter Reed National Military Medical Center as part of the Multidrug-Resistant Organism Repository and Surveillance Network.
The findings revealed that all 20 strains showed some level of resistance to QACs—the key active ingredient in most cleaning products—and 80% of them were fully resistant to QACs.
“This mechanism has been effective for a century, essentially dismantling the outer and inner membranes of a pathogen,” Wuest remarks. “We were taken aback by the degree to which this is no longer effective.”
Wuest hypothesizes that improper usage of cleaning agents might contribute to this resistance.
“QACs do not provide immediate results,” he clarifies. “After application, it is crucial to wait four or five minutes before wiping these cleaning agents away. Correct concentration is equally vital. If misused, certain bacteria may survive, which can foster resistance.”
Increased utilization of cleaning agents during the COVID-19 pandemic may have also allowed P. aeruginosa and other resilient pathogens more chances to build resistance, he adds.
An innovative method that works exceptionally well
In the current study, the researchers also investigated the resistance of multidrug-resistant P. aeruginosa strains to a new quaternary phosphonium compound (QPC) created in the Wuest and Minbiole laboratories. The results indicated that this new compound effectively killed all 20 resistant strains of P. aeruginosa.
“It is surprisingly effective, even at lower concentrations,” says Vargas-Cuebas.
The team demonstrated that their innovative QPC operates not by breaching the protective outer membrane of P. aeruginosa but by passing through it and specifically targeting the inner cellular membrane.
“It’s counterintuitive,” Wuest observes. “One might think that a conventional biocidal method targeting both membranes would be more successful in exterminating P. aeruginosa. However, we currently do not understand why our QPC compound is more effective by diffusing through the outer membrane and focusing on the inner membrane. It almost feels like magic.”
The researchers confirmed that this same mechanism is responsible for the effectiveness of two commercial antiseptics: octenidine, commonly used in European hospitals, and chlorhexidine, often found in mouthwashes.
Wuest and his team plan to further explore how this newly identified action may combat various pathogens and how these insights could lead to new biocides and enhanced cleaning strategies in healthcare environments.
“Our research is opening avenues for essential innovations in disinfectant development,” Wuest concludes.
Additional contributors to the paper include Emory graduate student Marina Michaud, undergraduate Shehreen Siddiqui, and PhD graduates Ryan Allen and Kelly Morrison-Lewis.
This research was supported by funding from the National Institutes of Health.
