The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic ...resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25 × and 0.5 × Minimum Inhibitory Concentration, MIC) or inhibitory (1 × and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20–167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment.
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•Increasing concentrations of QACs induced irreversible antibiotic resistance•Twin-chained DDAC induced higher resistance and more mutations than mono-chained BAC•17 mutated genes were identified with direct correlations with antibiotic resistance.•Mutations causing upregulated efflux pump was a main antibiotic resistance mechanism.
Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are standard indexes for determining disinfection effectiveness. Nevertheless, they are static values disregarding ...the kinetics at sub-MIC concentrations where adaptation, growth, stationary, and death phases can be observed. The understanding of these dynamic mechanisms is crucial to designing effective disinfection strategies. In this study, we studied the 48 h kinetics of
and
cells exposed to sub-MIC concentrations of didecyldimethylammonium chloride (DDAC). Two mathematical models were employed to reproduce the experiments: the only-growth classical logistic model and a mechanistic model including growth and death dynamics. Although both models reproduce the lag, exponential and stationary phases, only the mechanistic model is able to reproduce the death phase and reveals the concentration dependence of the bactericidal/bacteriostatic activity of DDAC. This model could potentially be extended to study other antimicrobials and reproduce changes in optical density (OD) and colony-forming units (CFUs) with the same parameters and mechanisms of action.
The use of quaternary ammonium compounds (QACs) as disinfectants has increased tremendously in the COVID-19 pandemic to inactivate Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV2). ...Dialkyldimethylammonium halides represent a frequently used type among QACs. Different halide anions, each ionically linked to the same quaternary ammonium cation, show clear differences in biocidal activity, toxicity and allergic potential. Likewise, the alkyl chain length at the ammonium cation induces different biocidal efficacy and toxicology. Therefore, the object of this research was to develop a rapid and reliable method for the detection of ammonium cation and halide anion in a single analytical run. For that purpose, a gas chromatography mass spectrometry (GC/MS) method was developed for QACs of the dialkyldimethylammonium type. Pyrolytic conversion of the QACs in the injector port of the gas chromatograph into volatile molecule species allows fast and reliable subsequent GC/MS analysis. The developed method is suited for the determination of both the quaternary ammonium cation and the corresponding halide anion in a single gas chromatographic run. The application of this method to bulk material and standard material of explicitly specified didecyldimethylammonium chloride revealed deviations from the manufacturer’s specifications in a range up to four-fifths. Furthermore, didecyldimethylammonium chloride was detected in a disinfectant that does not comply with the labeling requirement for biocidal ingredients. With the method presented, results can be obtained for disinfectants with minimum effort within seven minutes.
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•Development of a new analytical method for quaternary ammonium compounds (QACs).•Gas chromatographic mass spectrometric test of biocidal QACs by pyrolytic conversion.•Detection of QACs and corresponding halides in a single gas chromatographic run.•Quality control of didecyldimethyl ammonium chloride (DDAC) in disinfectants.•Revealment of significant deviations of DDAC bulk samples from the specifications.
The foodborne pathogen,
, (
), frequently undergoes selection pressure associated with the extensive use of disinfectants, such as quaternary ammonium compounds, which are widely used in food ...processing plants. The repeated exposure to sub-inhibitory biocide concentrations can induce increased tolerance to these compounds, but can also trigger the development of antibiotic resistance, and both increase the risk of food contamination and persistence in food production environments. Although the acquisition of genes can explain biocide tolerance, the genetic mechanisms underlying the adaptive cross-resistance to antibiotics remain unclear. We previously showed that repeated exposure to benzalkonium chloride (BC) and didecyldimethyl ammonium chloride (DDAC) led to reduced susceptibility to ciprofloxacin in
strains from diverse sources. Here, we compared the genomes of 16 biocide-adapted and 10 parental strains to identify the molecular mechanisms of fluoroquinolone cross-resistance. A core genome SNP analysis identified various mutations in the transcriptional regulator
(lmo2088) for 94% of the adapted strains and mutations in other effectors at a lower frequency. FepR is a local repressor of the MATE fluoroquinolone efflux pump FepA. The impact of the mutations on the structure and function of the protein was assessed by performing
prediction and protein homology modeling. Our results show that 75% of the missense mutations observed in
are located in the HTH domain of the protein, within the DNA interaction site. These mutations are predicted to reduce the activity of the regulator, leading to the overexpression of the efflux pump responsible for the ciprofloxacin-enhanced resistance.
Background
The use of disinfectants is part of the everyday life of people, especially in the medical profession. During the coronavirus disease 2019 (COVID‐19) pandemic, the use of disinfectants ...continues to increase and is of fundamental importance in infection control.
Objectives
To determine the frequency of sensitization and the value of patch testing to didecyldimethylammonium chloride (DDAC) and the alcohols ethanol, 1‐propanol, and isopropanol.
Methods
Clinical patch test data of 145 patients with suspected contact allergy to disinfectants were retrospective analysed.
Results
Among the 145 patients patch tested with the different alcohols, only one nurse was detected with a possible allergy to 1‐propanol. Additional patch testing in 84 patients with DDAC 0.05% resulted in five patients with weakly positive reactions only, without clinical relevance. Patch testing with DDAC 0.03% showed no positive reactions at all on day 3 readings.
Conclusions
DDAC and alcohols are rarely responsible for allergic contact dermatitis. The accused products of the patients should be checked for other allergens and further additives with skin‐irritating properties. Individual susceptibility and mishandling of the disinfectants should be considered.
Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a ...component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.
•The global use of disinfectants is rapidly increasing due to the pandemic of COVID-19.•We studied toxicity of didecyldimethylammonium chloride (DDAC) in vivo and in vitro.•Cell viability decreased accompanying impairment of intracellular components.•Formation of a lamellar body-like structure was observed in DDAC-treated cells and mice.•Chronic fibrotic pulmonary lesions was observed in mice instilled twice with DDAC.
The reuse of decontaminated disposable medical face masks can contribute to reducing the environmental burden of discarded masks. This research is focused on the effect of household and laboratory ...washing at 50 °C on the quality and functionality of the nonwoven structure of polypropylene medical masks by varying the washing procedure, bath composition, disinfectant agent, and number of washing cycles as a basis for reusability. The barrier properties of the medical mask were analyzed before and after the first and fifth washing cycle indirectly by measuring the contact angle of the liquid droplets with the front and back surface of the mask, further by measuring air permeability and determining antimicrobial resistance. Additional analysis included FTIR, pH of the material surface and aqueous extract, as well as the determination of residual substances-surfactants-in the aqueous extract of washed versus unwashed medical masks, while their aesthetic aspect was examined by measuring their spectral characteristics. The results showed that household washing had a stronger impact on the change of some functional properties, primarily air permeability, than laboratory washing. The addition of the disinfectant agent, didecyldimethylammonium chloride, contributes to the protective ability and supports the idea that washing of medical masks under controlled conditions can preserve barrier properties and enable reusability.