Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance

Pereira, Beatriz Merchel Piovesan; Tagkopoulos, Ilias

doi:10.1128/aem.00377-19

Cited by 221 publications

(191 citation statements)

References 85 publications

(132 reference statements)

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“…This phenomenon suggests that phenotypic changes are most likely based on a genetically determined tolerance mechanism rather than on a short-term phenotypic adaptation. Several mechanisms of BC resistance have been recently reviewed [18]. However, the…”

Section: Discussionmentioning

confidence: 99%

“…Several mechanisms of BC resistance have been recently reviewed [18]. However, the effect of BC adaptation on the development of a VBNC state has not been addressed in L. monocytogenes so far.…”

Section: Discussionmentioning

confidence: 99%

“…Various stress conditions have been identified to induce the VBNC state in L. monocytogenes, including chlorine-based sanitizing treatments [15] and non-ionic surfactants combined with inorganic salts [13]. Quaternary ammonium compounds (QACs), such as benzalkonium chloride (BC), are widely used as biocides for the disinfection of surfaces, including food production environments [18,19]. The alkyl chain of QACs perturbs and disrupts the microbial membrane bilayer and its charge distribution [20].…”

Section: Introductionmentioning

confidence: 99%

“…The alkyl chain of QACs perturbs and disrupts the microbial membrane bilayer and its charge distribution [20]. Microbial mechanisms of tolerance and resistance towards QACs include changes in the overall membrane composition, downregulation of porins, overexpression or modification of efflux pumps, horizontal gene transfer of resistance-associated genes, biofilm formation, and biodegradation of QACs [18]. Exposure of L. monocytogenes to progressively increasing BC concentrations frequently leads to BC adaptation, which can often be attributed to shifts in the efflux pump activity [19,21,22].…”

Section: Introductionmentioning

confidence: 99%

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Benzalkonium Chloride Induces a VBNC State in Listeria monocytogenes

et al. 2020

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The objective of our study was to investigate the effects of benzalkonium chloride (BC) adaptation of L. monocytogenes on the susceptibility to antimicrobial agents and on the viable but non culturable (VBNC) state of the bacterial cells. We adapted L. monocytogenes SLCC2540 to BC by applying BC below minimum inhibitory concentration (MIC) to above minimum bactericidal concentration (MBC). The culturable fractions and the susceptibility of adapted and parental cells to BC were assessed. In addition, cell membrane permeability and glucose uptake were analyzed by multi parametric flow cytometry using the fluorescent agents SYTO9, propidium iodide, and 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG). Adapted cells displayed a two-fold MIC increase of BC and reduced antibiotic susceptibility. At high BC concentrations, the decrease in the number of colony forming units was significantly lower in the population of adapted cells compared to parental cells. At the same time, the number of metabolically active cells with intact membranes was significantly higher than the number of culturable cells. Growth-independent viability assays revealed an adapted subpopulation after BC application that was not culturable, indicating increased abundance of viable but nonculturable (VBNC) cells. Moreover, adapted cells can outcompete non-adapted cells under sublethal concentrations of disinfectants, which may lead to novel public health risks.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzalkonium Chloride Induces a VBNC State in Listeria monocytogenes

et al. 2020

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“…Disinfection is the most common method used to eliminate L. monocytogenes from the food-processing environment [3]. Quaternary ammonium compounds (QACs), such as benzalkonium chloride (BAC), are widely used as disinfectants in food-processing areas [4][5][6]. The presence of BAC in the environment is a growing public health concern, as BAC can select not only for biocide resistance but also for clinically relevant antibiotic resistance [7].…”

Section: Introductionmentioning

confidence: 99%

Strain and Growth Conditions may Regulate Resistance of Listeria monocytogenes Biofilms to Benzalkonium Chloride

et al. 2020

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Listeria monocytogenes is one of the main foodborne pathogens. The formation of biofilms by L. monocytogenes contributes to its resistance to disinfectants, which represents a serious risk for food production plants. The aim of this study was to compare the effect of sub-inhibitory concentrations of benzalkonium chloride (BAC) (1.25 or 2.5 mg/L) on biofilm production and on biofilm reduction after exposure to an inhibitory concentration of BAC (1280 mg/L) in two isogenic L. monocytogenes strains: the BAC-sensitive wild-type strain S2-1 and its BAC-resistant mutant derivative S2BAC, which presented a multidrug resistance phenotype. The biofilm-forming ability of the strains under different BAC concentrations was evaluated by the resazurin method using polystyrene microplates. The biofilm reduction after BAC exposure was evaluated by using stainless steel coupons (SSCs). When the resazurin method was used, S2BAC produced significantly more biofilm in the presence of a sub-inhibitory concentration of BAC compared to that in the culture medium without BAC (p < 0.05). When the SSC method was used, the presence of sub-inhibitory concentrations of BAC resulted in a higher resistance of the biofilm for S2BAC compared to that in the culture medium without BAC (p < 0.05). This was not observed with the sensitive S2-1 strain. These results suggest that biofilm behavior depends on the strain and sub-inhibitory concentrations of disinfectants and may explain the ability of certain isolates to persist in niches of food processing plants.

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Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering

Yang,

Yiannias,

Voss

et al. 2023

JAMA Dermatol

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ImportancePatients are frequently copositive for multiple allergens simultaneously, either due to chemical similarity or simultaneous sensitization. A better understanding of copositivity groups would help guide contact avoidance.ObjectiveTo use patient data to systematically determine copositivity groups in the Mayo Clinic Standard Series.Design, Setting, and ParticipantsIn this retrospective cross-sectional analysis, the Mayo Clinic patch test database was queried for pairwise copositivity rates in the 80 allergen Mayo Clinic Standard Series between 2012 and 2021. Data were collected from 3 tertiary care sites of the Mayo Clinic Contact Dermatitis Group and a total of 5943 patients were included, comprising all patients undergoing patch testing to the Mayo Clinic Standard Series allergens.Main Outcomes and MeasuresCopositivity rates between every 2 allergens in the 80-allergen Mayo Clinic Standard Series were estimated. After background correction, copositivity rates were analyzed using unsupervised hierarchical clustering to systematically identify copositivity groups in an unbiased manner.ResultsOverall, 394 921 total patches were applied to 5943 patients (4164 [70.1%] women, 1776 [29.9%] men, with a mean [SD] age of 52.3 [18.8] years ), comprising 9545 positive reactions. After background correction based on overall positivity rates, hierarchical clustering revealed distinct copositivity groups. Many were supported by prior literature, including formaldehyde releasers, cobalt-nickel-potassium dichromate, acrylates, 3-dimethylaminopropylamine-amidoamine-oleamidopropyl dimethylamine, alkyl glucosides, budesonide-hydrocortisone-17-butyrate, certain fragrances, compositae-sesquiterpene lactone mix, mercapto mix-mercaptobenzothiazole, carba mix-thiuram mix, and disperse orange-p-phenylenediamine. However, novel associations were also found, including glutaraldehyde-sorbitan sesquioleate, benzalkonium chloride-neomycin-bacitracin, bronopol-methylchloroisothiazolinone-methylisothiazolinone, and benzoic acid-iodopropynyl butylcarbamate.Conclusions and RelevanceThis retrospective cross-sectional analysis found that copositivity rates varied between allergens; allergens with extremely high positivity rates demonstrated nonspecific copositivity to multiple other allergens. Background correction based on positivity rates followed by hierarchical clustering confirmed prior known copositivity groups, contaminants and/or excipients leading to copositivity, and novel associations to guide contact avoidance.

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Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance

Cited by 221 publications

References 85 publications

Benzalkonium Chloride Induces a VBNC State in Listeria monocytogenes

Benzalkonium Chloride Induces a VBNC State in Listeria monocytogenes

Strain and Growth Conditions may Regulate Resistance of Listeria monocytogenes Biofilms to Benzalkonium Chloride

Systematic Identification of Copositivity Groups in Standard Series Patch Testing Through Hierarchical Clustering

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