Widely Used Benzalkonium Chloride Disinfectants Can Promote Antibiotic Resistance

Abstract

While misuse of antibiotics has clearly contributed to the emergence and proliferation of resistant bacterial pathogens with major health consequences, it remains less clear if the widespread use of disinfectants, a different class of biocides than antibiotics such as benzalkonium chlorides (BAC), has contributed to this problem. Here, we provide evidence that exposure to BAC co-selects for antibiotic-resistant bacteria, and describe the underlying genetic mechanisms. BAC-fed bioreactors inoculated with river sediment selected for several bacterial taxa, including the opportunistic pathogen , that were more resistant to several antibiotics compared to their counterparts in a control (no BAC) bioreactor. Metagenomic analysis of the bioreactor microbial communities, confirmed by gene cloning experiments with the derived isolates, suggested that integrative and conjugative elements encoding a BAC efflux pump together with antibiotic resistance genes were responsible for these results. Further, exposure of the isolates to increasing concentrations of BAC selected for mutations in (polymyxin resistance) and physiological adaptations that contributed to higher tolerance to polymyxin B and other antibiotics. Physiological adaptations included, for example, the overexpression of multidrug efflux pump genes when BAC was added in the growth medium at sub-inhibitory concentrations. Collectively, our results demonstrated that disinfectants can promote antibiotic resistance via several mechanisms, and highlight the need to remediate (degrade) disinfectants in non-target environments to further restrain the spread of antibiotic resistant bacteria. Benzalkonium chlorides (BAC) are broadly used biocides in disinfectant solutions. Disinfectants are widely used in food processing lines, domestic households, and pharmaceuticals products, and are typically designed to have a different mode of action than antibiotics in order to not interfere with the use of the latter. Whether or not exposure to BAC makes bacteria more resistant to antibiotics remains, however, an unresolved issue of obvious practical consequences for public health. Using an integrated approach that combined metagenomics of natural microbial communities with gene cloning experiments with isolates and experimental evolution assays, we show that the widely used benzalkonium chloride disinfectants can promote clinically-relevant antibiotic resistance. Therefore, more attention should be given to the usage of these disinfectants, and their fate in non-target environments should be more tightly monitored.

Demonstrating the persistent antibacterial efficacy of a hand sanitizer containing benzalkonium chloride on human skin at 1, 2, and 4 hours after application

“…They concluded that the persistent populations on the cannery lines were not inherently more tolerant to the disinfectant but that other factors (ie, surface attachment, biofilm formation, and growth rate) were likely responsible for their ability to persist in the disinfectant-treated environment. Kim et al (2018) 17 examined the impact of continuous exposure to BK on bacterial populations isolated from contaminated river sludge. The sediment samples were maintained for extended periods (3 years) in bioreactors containing nutrient medium and increasing concentrations of BK or nutrient medium alone.…”

Granular parakeratosis is a reaction pattern in hyperkeratotic flexural erythema

“…This paper as well as a few other publications highlight the detrimental effects of using benzalkonium chloride in laundry detergents and bath oils. [3][4][5] This would be an opportune moment for the Australasian College of Dermatologists and other similar scientific bodies to bring this to the notice of the public, detergent industry stake holders and relevant government agencies, with a view to stopping the practice of adding unnecessary antifungal and antibacterial additives to laundry detergents. Such additives do not have any proven benefit in preventing infections.…”

“…4 Only once the public has mastered these basic sun protection modalities can the medical community introduce more novel and experimental modalities of sun protection. 5 Vangelis George Kanellis 1 | Alice Louise Kanellis 2 | Lena Von Schuckmann 3 |…”

Rapid, Low-Cost Detection of Water Contaminants Using RegulatedIn VitroTranscription

“…We next sought to demonstrate that ROSALIND could be used to sense two PPCP compounds: (1) salicylate, a widely used compound in personal care products [48] that has been shown to bind to the Staphylococcus aureus MarR-family aTF SAR2349 [53], and (2) benzalkonium chloride, a widely used disinfectant that can promote antimicrobial resistance [54], and has been shown to bind to the Staphylococcus aureus TetR-family aTF QacR [55]. When these purified aTFs and the corresponding operator-containing DNA constructs were included in ROSALIND reactions, we were able detect these two PPCP compounds at a high micromolar to low millimolar range ( Fig.…”