Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection.
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ABSTRACT:
SUBMITTER: Nordholt N
PROVIDER: S-EPMC8611074 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBiocide disinfectants are essential tools in infection control, but their use can inadvertently contribute to emergence of antibiotic-resistant bacteria. In this study we systematically examine the effect of the biocide benzalkonium chloride, which is primarily used for surface disinfection but is also present as a preservative in many consumer products, on the activity of aminoglycoside antibiotics in Acinetobacter baumannii.MethodsThe effect of subinhibitory BAC on aminoglycoside treatment of A. baumannii ATCC17978 was investigated using time-to-kill assays, MIC determination, directed evolution experiments, fluctuation tests and labelled gentamicin accumulation assays. Further MIC determinations and directed evolution experiments were performed with additional Gram-negative ESKAPE pathogens.FindingsIn A. baumannii ATCC17978, BAC prevents gentamicin killing and drastically increases the frequency at which resistant mutants emerge, through reducing intracellular antibiotic accumulation. BAC also increases the MIC of multiple aminoglycoside antibiotics (kanamycin, tobramycin, streptomycin, gentamicin and amikacin). BAC promotes the emergence of mutants with reduced gentamicin susceptibility in other Gram-negative ESKAPE pathogens but does not always alter the MIC. These effects occur at BAC concentrations which are similar to residual levels in high-use environments, and just below the concentration range for BAC when used as a preservative in eye drops and ear drops.InterpretationOur results suggest that subinhibitory BAC has the potential to antagonise aminoglycoside activity and promote the emergence of bacterial mutants with reduced susceptibility. We suggest that the extremely widespread use of BAC in clinical and home settings and its long half-life mean there is potential for these interactions to occur in the environment, or in patients who use BAC-containing products while taking aminoglycosides to treat skin, eye or ear infections, although such co-exposure is likely to be rare. We suggest that biocide stewardship is needed to prevent the types of exposure that can contribute to antibiotic resistance.FundingThis work was funded by the National Health and Medical Research Council of Australia. The funders had no role in study design, interpretation or decision to publish.
| S-EPMC8577336 | biostudies-literature
Project description:Benzalkonium chloride (BC) is a commonly used disinfectant and preservative. This study describes changes in expression level on the transcriptomic and proteomic level for Escherichia coli K12 gradually adapted to a tolerance level towards BC of 7-8 times the initial MIC. Results from DNA arrays and two-dimensional (2-DE) gel electrophoresis for global gene and protein expression studies were confirmed by real time quantitative PCR. Peptide mass fingerprinting by MALDI-TOF MS was used to identify differentially expressed proteins. Changes in expression level in adapted cells were shown for porins, drug transporters, glycolytic enzymes, ribosomal subunits and several genes and proteins involved in protection against oxidative stress and antibiotics. Adapted strains showed increased tolerance to several antibiotics. In conclusion, E. coli K12 adapted to higher tolerance to BC, acquired several general resistance mechanisms including responses normally related to the multiple antibiotic resistance (Mar) regulon and protection against oxidative stress. The results revealed that BC treatment might result in superoxide stress in E. coli. Keywords: Study of resistance mechanism
2007-05-23 | GSE6712 | GEO
Project description:A comprehensive comparative analysis of antifungal potential of benzalkonium chloride and newly synthesized fullerenol/benzalkonium chloride nanocomposite was conducted to assess the possible impact of carbon-based nanocarrier on antimicrobial properties of the commonly used biocide. Physical characterization of synthesized nanocomposite showed zeta potential of +37.4 mV and inhomogeneous particles size distribution, with nanocomposite particles' dimensions within 30-143 nm and maximum number of particles at 44 nm. The effect of pure and fullerenol nanocarrier-bound biocide was evaluated in eight Aspergillus species. In mycelial growth assay, nanocomposite was more potent, as fungicidal effect of 1.04/0.6 μg mL(-1) was obtained in all but one of the isolates (A. niger), while proportional concentration of pure biocide (0.6 μg mL(-1)) completely inhibited mycelial growth of only three Aspergillus species. However, conidia appear to be less susceptible to nanocomposite treatment, as lower fungistatic (MIC) and fungicidal (MFC) concentrations were obtained with biocide alone (MIC in range from 0.03 to 0.15 μg mL(-1) and MFC from 0.075 to 0.45 μg mL(-1)). To a different degree, both substances stimulated aflatoxin B1 production and inhibited ochratoxin A synthesis. Very low mycelium biomass yield, in range from 1.0 to 3.0 mg dry weight, was documented in both biocide and nanocomposite enriched medium.
| S-EPMC4532958 | biostudies-other
Project description:Controlling the food-borne pathogen Listeria (L.) monocytogenes is of great importance from a food safety perspective, and thus for human health. The consequences of failures in this regard have been exemplified by recent large listeriosis outbreaks in the USA and Europe. It is thus particularly notable that tolerance to quaternary ammonium compounds such as benzalkonium chloride (BC) has been observed in many L. monocytogenes strains. However, the molecular determinants and mechanisms of BC tolerance of L. monocytogenes are still largely unknown. Here we describe Tn6188, a novel transposon in L. monocytogenes conferring tolerance to BC. Tn6188 is related to Tn554 from Staphylococcus (S.) aureus and other Tn554-like transposons such as Tn558, Tn559 and Tn5406 found in various Firmicutes. Tn6188 comprises 5117 bp, is integrated chromosomally within the radC gene and consists of three transposase genes (tnpABC) as well as genes encoding a putative transcriptional regulator and QacH, a small multidrug resistance protein family (SMR) transporter putatively associated with export of BC that shows high amino acid identity to Smr/QacC from S. aureus and to EmrE from Escherichia coli. We screened 91 L. monocytogenes strains for the presence of Tn6188 by PCR and found Tn6188 in 10 of the analyzed strains. These isolates were from food and food processing environments and predominantly from serovar 1/2a. L. monocytogenes strains harboring Tn6188 had significantly higher BC minimum inhibitory concentrations (MICs) (28.5 ± 4.7 mg/l) than strains without Tn6188 (14 ± 3.2 mg/l). Using quantitative reverse transcriptase PCR we could show a significant increase in qacH expression in the presence of BC. QacH deletion mutants were generated in two L. monocytogenes strains and growth analysis revealed that ?qacH strains had lower BC MICs than wildtype strains. In conclusion, our results provide evidence that Tn6188 is responsible for BC tolerance in various L. monocytogenes strains.
| S-EPMC3788773 | biostudies-literature
Project description:Disinfectants are routinely used in human environments to control and prevent the transmission of microbial disease, and this is particularly true during the current COVID-19 crisis. However, it remains unclear whether the increased disinfectant loadings to wastewater treatment plants facilitate the dissemination of antibiotic resistance genes (ARGs) in sewage sludge microbiomes. Here, we investigated the impacts of benzalkonium chlorides (BACs), widely used disinfectants, on ARGs profiles and microbial community structures in sewage sludge by using high-throughput quantitative PCR and Illumina sequencing. A total of 147 unique ARGs and 39 mobile genetic elements (MGEs) were detected in all sewage sludge samples. Our results show that exposure to BACs disinfectants at environmentally relevant concentrations significantly promotes both the diversity and absolute abundance of ARGs in sludge microbiomes, indicating the co-selection of ARGs by BACs disinfectants. The enrichment of ARGs abundance varied from 2.15-fold to 3.63-fold compared to controls. In addition, BACs exposure significantly alters bacterial and protistan communities, resulting in dysbiosis of the sludge microbiota. The Mantel test and Procrustes analysis confirm that bacterial communities are significantly correlated with ARGs profiles under BACs treatments. The structural equation model explains 83.8 % of the total ARGs variation and further illustrates that the absolute abundance of MGEs exerts greater impacts on the variation of absolute abundance of ARGs than microbial communities under BACs exposure, suggesting BACs may promote antibiotic resistance by enhancing the horizontal gene transfer of ARGs across sludge microbiomes. Collectively, our results provide new insights into the proliferation of antibiotic resistance through disinfectant usage during the pandemic and highlight the necessity to minimize the environmental release of disinfectants into the non-target environment for combating antibiotic resistance.
| S-EPMC9830840 | biostudies-literature
Project description:Purpose: Adenoviral conjunctivitis is the most common cause of conjunctivitis worldwide with no approved antiviral treatment. Benzalkonium chloride (BAK) is a common preservative in ophthalmic medications and is the active ingredient in some skin disinfectants and hand sanitizers. BAK is known to be effective in killing bacteria and enveloped viruses; however, its activity against ocular types of nonenveloped adenoviruses (Ads) is unknown. The goal was to determine whether BAK is an effective antiviral agent against common human ocular types of adenovirus in vitro. Methods: The direct inactivating activity of BAK was determined by incubating several human adenovirus types with BAK concentrations of 0.001%, 0.003%, 0.005%, 0.01%, 0.1%, and 0% for 1 h at 33°C. Resulting adenovirus titers were determined after treatment. Decreases in titers of ≥3 Log10 were considered virucidal, while decreases in titers of <1 Log10 were considered ineffective. Results: BAK 0.1% was virucidal for Ad3, Ad5, Ad7a, Ad19/64, and Ad37, while it reduced titers >1 Log10, but <3 Log10 for Ad4 and Ad8. Decreases in titers >1 Log10 were demonstrated for BAK 0.003%, 0.005%, and 0.01% for Ad5 only. Decreases in titers for the other adenovirus types for those concentrations were ≤0.53 Log10. 0.001% BAK produced minimal decreases in titers for all types. Conclusions: BAK, at 0.01% or less was not consistently effective as an antiviral against adenovirus, but higher concentrations, such as 0.1%, should be further investigated as a possible topical treatment for adenoviral ocular infections, providing ocular toxicity is not an issue.
| S-EPMC6588108 | biostudies-literature
Project description:Optimal disinfection protocols are fundamental to minimize bacterial resistance to the compound applied, or cross-resistance to other antimicrobials such as antibiotics. The objective is twofold: guarantee safe levels of pathogens and minimize the excess of disinfectant after a treatment. In this work, the disinfectant dose is optimized based on a mathematical model. The model explains and predicts the interplay between disinfectant and pathogen at different initial microbial densities (inocula) and dose concentrations. The study focuses on the disinfection of Escherichia coli with benzalkonium chloride, the most common quaternary ammonium compound. Interestingly, the specific benzalkonium chloride uptake (mean uptake per cell) decreases exponentially when the inoculum concentration increases. As a consequence, the optimal disinfectant dose increases exponentially with the initial bacterial concentration.
| S-EPMC6028699 | biostudies-literature
Project description:INTRODUCTION:The preservative benzalkonium chloride (BAK) is used to preserve several topical, intraocular pressure (IOP)-lowering glaucoma medications but can cause tolerability concerns that may lead to decreased adherence to treatment and ultimately diminish the effectiveness of IOP control. The study aimed to determine the efficacy and tolerability of BAK-free travoprost preserved with polyquaternium-1 in glaucoma patients switched from BAK-preserved latanoprost or bimatoprost. METHODS:This 12-week, open-label study was conducted in Europe between December 2011 and February 2013. We enrolled adult patients with open-angle glaucoma or ocular hypertension who were receiving BAK-preserved latanoprost 0.005% or bimatoprost 0.01% and, in the opinion of the investigator, would benefit from transition to BAK-free travoprost 0.004% preserved with polyquaternium-1 because of tolerability concerns. Assessments included IOP, proportion of patients with IOP ?18 mmHg, ocular surface status, hyperemia, patient treatment preference, and adherence. Adverse events were recorded throughout the study. RESULTS:Of the 202 patients screened, 187 patients were included in the intent-to-treat population (mean age, 66.6 years; range, 19-90 years). The mean IOP significantly reduced from baseline (17.0 mmHg) to week 6 (mean change, -1.17 mmHg; P<0.001) and week 12 (-1.16 mmHg; P<0.001). At week 12, more patients achieved IOP ?18 mmHg (81.2% versus 73.3% at baseline), and ocular surface disease severity improved from baseline to week 12. Most patients preferred BAK-free travoprost (74.9%) versus their previous medication and were very confident in their adherence (84.1%). Reduced visual acuity and eye pruritus were the most common adverse events (2.5% each). CONCLUSION:BAK-free travoprost 0.004% preserved with polyquaternium-1 was efficacious and well tolerated and may be an advantageous prostaglandin analog option for patients with open-angle glaucoma or ocular hypertension who are intolerant to BAK-preserved latanoprost or bimatoprost.
| S-EPMC5085282 | biostudies-literature
Project description:Listeria monocytogenes is an important food-borne pathogen that can persist in food processing environments and thus contaminate food products. Benzalkonium chloride (BC) is a common disinfectant widely used in food industry. Selective pressure associated with exposure to BC may result in adaptation to this agent in L. monocytogenes. In this study, the effect of BC adaptation on susceptibility to antimicrobial agents and tolerance to environmental stresses, as well as the role of efflux pumps in BC adaptation were investigated in Listeria monocytogenes. Exposure of L. monocytogenes to progressively increasing concentrations of BC led to adaptation not only to BC but also to several other antimicrobial agents with different modes of action, including cefotaxime, cephalothin, ciprofloxacin, and ethidium bromide (EtBr), indicating that the disinfectant BC has the ability to select for antibiotic resistance. Reserpine, an efflux pump inhibitor, reduced minimum inhibitory concentrations (MICs) of cephalosporins, ciprofloxacin, and EtBr in BC adapted strains, indicating that efflux pumps are involved in cross-adaptation to these antimicrobial agents. Our results showed that expression levels of the efflux pump MdrL in the BC adapted strains increased significantly relative to the corresponding wild-type strains (P < 0.05), with the highest increase in one BC adapted strain named HL06BCA. Moreover, the knockout mutant HL06BCAΔmdrL showed impaired growth compared to that of HL06BCA when exposed to 2 μg/ml of BC. It suggests that efflux pump MdrL is associated with BC adaptation in L. monocytogenes. However, we did not find mdrL to be associated with cross-adaptation to cephalosporins, ciprofloxacin, and EtBr in HL06BCA. Additionally, increased sensitivity to acid, alkali, osmotic, ethanol, and oxidative stresses was observed in most strains after repeated exposure to BC. These results suggest rotation of different disinfectant is helpful to maintain high effectiveness of BC toward L. monocytogenes and ethanol and hydrogen peroxide are at least the appropriate candidates.
| S-EPMC6279922 | biostudies-literature
Project description:BackgroundHand hygiene is critical to lower the potential for the spread of SARS-CoV-2 and other infectious agents by direct contact. When running water and soap are not available for hand hygiene, ethanol-based hand sanitizers are currently the recommended standard of care [1-3]. Though recently published data showed comparable in vitro effectiveness of benzalkonium chloride (BAK)-based and ethanol-based hand sanitizers against SARS-CoV-2 virus, a paucity of peer-reviewed data on the effectiveness of these formulations against other types of infective coronaviruses remains. This work assessed human coronavirus HCoV-229E (genus Alphacoronavirus) concurrently with SARS-CoV-2, Isolate USA-WA1/2020 (genus Betacoronavirus) to fill this gap.MethodsThe test was conducted according to EN14476:2013-A2:2019 [EN14476] Quantitative Suspension Test for the Evaluation of Virucidal Activity in the Medical Area [4]. Two BAK-based hand sanitizers, five ethanol-based hand sanitizers, and an 80% ethanol reference formulation were tested for antiviral activity against SARS-CoV-2 and HCoV-229E at 15- and 30- second contact times.ResultsBoth SARS-CoV-2 and HCoV-229E were reduced by greater than 4.00-log10 within 15 seconds of contact. Virus decay constants (k) following first-order kinetics were similar for BAK and ethanol-based formulations against both test viruses. The SARS-CoV-2 results reported herein mirrored previous data reported by Herdt et al. (2021).ConclusionBAK and ethanol hand sanitizer formulations inactivate SARS-CoV-2 and HCoV-229E at similar rates. This data supports previously published effectiveness data for both chemistries and indicates that additional coronavirus strains and variants would demonstrate similar inactivation trends.
| S-EPMC10266983 | biostudies-literature