Prediction and validation of common targets in atherosclerosis and non-small cell lung cancer influenced by atorvastatin.

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

New roles for Bacillus thuringiensis in the removal of environmental pollutants.

For a long time, the well-known Gram-positive bacterium Bacillus thuringiensis (Bt) has been extensively studied and developed as a biological insecticide for Lepidoptera and Coleoptera pests due to its ability to secrete a large number of specific insecticidal proteins. In recent years, studies have found that Bt strains can also potentially biodegrade residual pollutants in the environment. Many researchers have isolated Bt strains from multiple sites polluted by exogenous compounds and characterized and identified their xenobiotic-degrading potential. Furthermore, its pathway for degradation was also investigated at molecular level, and a number of major genes/enzymes responsible for degradation have been explored. At present, a variety of xenobiotics involved in degradation in Bt have been reported, including inorganic pollutants (used in the field of heavy metal biosorption and recovery and precious metal recovery and regeneration), pesticides (chlorpyrifos, cypermethrin, 2,2-dichloropropionic acid, etc.), organic tin, petroleum and polycyclic aromatic hydrocarbons, reactive dyes (congo red, methyl orange, methyl blue, etc.), and ibuprofen, among others. In this paper, the biodegrading ability of Bt is reviewed according to the categories of related pollutants, so as to emphasize that Bt is a powerful agent for removing environmental pollutants.

Microbial degradation as a powerful weapon in the removal of sulfonylurea herbicides.

Sulfonylurea herbicides have been widely used worldwide and play a significant role in modern agricultural production. However, these herbicides have adverse biological effects that can damage the ecosystems and harm human health. As such, rapid and effective techniques that remove sulfonylurea residues from the environment are urgently required. Attempts have been made to remove sulfonylurea residues from environment using various techniques such as incineration, adsorption, photolysis, ozonation, and microbial degradation. Among them, biodegradation is regarded as a practical and environmentally responsible way to eliminate pesticide residues. Microbial strains such as Talaromyces flavus LZM1, Methylopila sp. SD-1, Ochrobactrum sp. ZWS16, Staphylococcus cohnii ZWS13, Enterobacter ludwigii sp. CE-1, Phlebia sp. 606, and Bacillus subtilis LXL-7 can almost completely degrade sulfonylureas. The degradation mechanism of the strains is such that sulfonylureas can be catalyzed by bridge hydrolysis to produce sulfonamides and heterocyclic compounds, which deactivate sulfonylureas. The molecular mechanisms associated with microbial degradation of sulfonylureas are relatively poorly studied, with hydrolase, oxidase, dehydrogenase and esterase currently known to play a pivotal role in the catabolic pathways of sulfonylureas. Till date, there are no reports specifically on the microbial degrading species and biochemical mechanisms of sulfonylureas. Hence, in this article, the degradation strains, metabolic pathways, and biochemical mechanisms of sulfonylurea biodegradation, along with its toxic effects on aquatic and terrestrial animals, are discussed in depth in order to provide new ideas for remediation of soil and sediments polluted by sulfonylurea herbicides.

Pseudomonas aeruginosa based concurrent degradation of beta-cypermethrin and metabolite 3-phenoxybenzaldehyde, and its bioremediation efficacy in contaminated soils.

Beta-cypermethrin is one of the widely used pyrethroid insecticides, and problems associated with the accumulation of its residues have aroused public attention. Thus, there is an urgent need to effectively remove the beta-cypermethrin that is present in the environment. Biodegradation is considered a cost-effective and environmentally friendly method for removing pesticide residues. However, the beta-cypermethrin-degrading microbes that are currently available are not optimal. In this study, Pseudomonas aeruginosa PAO1 was capable of efficiently degrading beta-cypermethrin and its major metabolite 3-phenoxybenzaldehyde in water/soil environments. Strain PAO1 could remove 91.4% of beta-cypermethrin (50 mg/L) in mineral salt medium within 120 h. At the same time, it also possesses a significant ability to metabolize 3-phenoxybenzaldehyde-a toxic intermediate of beta-cypermethrin. The Andrews equation showed that the maximum substrate utilization concentrations of beta-cypermethrin and 3-phenoxybenzaldehyde by PAO1 were 65.3558 and 49.6808 mg/L, respectively. Box-Behnken design-based response surface methodology revealed optimum conditions for the PAO1 strain-based degradation of beta-cypermethrin as temperature 30.6 °C, pH 7.7, and 0.2 g/L inoculum size. The results of soil remediation experiments showed that indigenous micro-organisms helped to promote the biodegradation of beta-cypermethrin in soil, and beta-cypermethrin half-life in non-sterilized soil was 6.84 days. The bacterium transformed beta-cypermethrin to produce five possible metabolites, including 3-phenoxybenzyl alcohol, methyl 2-(4-hydroxyphenoxy)benzoate, diisobutyl phthalate, 3,5-dimethoxyphenol, and 2,2-dimethyl-1-(4-phenoxyphenyl)propanone. Among them, methyl 2-(4-hydroxyphenoxy)benzoate and 3,5-dimethoxyphenol were first identified as the intermediate products during the beta-cypermethrin degradation. In addition, we propose a degradation pathway for beta-cypermethrin that is metabolized by strain PAO1. Beta-cypermethrin could be biotransformed firstly by hydrolysis of its carboxylester linkage, followed by cleavage of the diaryl bond and subsequent metabolism. Based on the above results, P. aeruginosa PAO1 could be a potent candidate for the beta-cypermethrin-contaminated environmental bioremediation.

High-efficiency degradation of methomyl by the novel bacterial consortium MF0904: Performance, structural analysis, metabolic pathways, and environmental bioremediation.

Methomyl is a widely used carbamate pesticide, which has adverse biological effects and poses a serious threat to ecological environments and human health. Several bacterial isolates have been investigated for removing methomyl from environment. However, low degradation efficiency and poor environmental adaptability of pure cultures severely limits their potential for bioremediation of methomyl-contaminated environment. Here, a novel microbial consortium, MF0904, can degrade 100% of 25 mg/L methomyl within 96 h, an efficiency higher than that of any other consortia or pure microbes reported so far. The sequencing analysis revealed that Pandoraea, Stenotrophomonas and Paracoccus were the predominant members of MF0904 in the degradation process, suggesting that these genera might play pivotal roles in methomyl biodegradation. Moreover, five new metabolites including ethanamine, 1,2-dimethyldisulfane, 2-hydroxyacetonitrile, N-hydroxyacetamide, and acetaldehyde were identified using gas chromatography-mass spectrometry, indicating that methomyl could be degraded firstly by hydrolysis of its ester bond, followed by cleavage of the C-S ring and subsequent metabolism. Furthermore, MF0904 can successfully colonize and substantially enhance methomyl degradation in different soils, with complete degradation of 25 mg/L methomyl within 96 and 72 h in sterile and nonsterile soil, respectively. Together, the discovery of microbial consortium MF0904 fills a gap in the synergistic metabolism of methomyl at the community level and provides a potential candidate for bioremediation applications.

Cellular Response and Molecular Mechanism of Glyphosate Degradation by Chryseobacterium sp. Y16C.

Glyphosate is one of the most widely used herbicides worldwide. Unfortunately, the continuous use of glyphosate has resulted in serious environmental contamination and raised public concern about its impact on human health. In our previous study, Chryseobacterium sp. Y16C was isolated and characterized as an efficient degrader that can completely degrade glyphosate. However, the biochemical and molecular mechanisms underlying its glyphosate biodegradation ability remain unclear. In this study, the physiological response of Y16C to glyphosate stimulation was characterized at the cellular level. The results indicated that, in the process of glyphosate degradation, Y16C induced a series of physiological responses in the membrane potential, reactive oxygen species levels, and apoptosis. The antioxidant system of Y16C was activated to alleviate the oxidative damage caused by glyphosate. Furthermore, a novel gene, goW, was expressed in response to glyphosate. The gene product, GOW, is an enzyme that catalyzes glyphosate degradation, with putative structural similarities to glycine oxidase. GOW encodes 508 amino acids, with an isoelectric point of 5.33 and a molecular weight of 57.2 kDa, which indicates that it is a glycine oxidase. GOW displays maximum enzyme activity at 30 °C and pH 7.0. Additionally, most of the metal ions exhibited little influence on the enzyme activity except for Cu2+. Finally, with glyphosate as the substrate, the catalytic efficiency of GOW was higher than that of glycine, although opposite results were observed for the affinity. Taken together, the current study provides new insights to deeply understand and reveal the mechanisms of glyphosate degradation in bacteria.

Current insights into the microbial degradation of nicosulfuron: Strains, metabolic pathways, and molecular mechanisms.

Nicosulfuron is among the sulfonylurea herbicides that are widely used to control annual and perennial grass weeds in cornfields. However, nicosulfuron residues in the environment are likely to cause long-lasting harmful environmental and biological effects. Nicosulfuron degrades via photo-degradation, chemical hydrolysis, and microbial degradation. The latter is crucial for pesticide degradation and has become an essential strategy to remove nicosulfuron residues from the environment. Most previous studies have focused on the screening, degradation characteristics, and degradation pathways of biodegrader microorganisms. The isolated nicosulfuron-degrading strains include Bacillus, Pseudomonas, Klebsiella, Alcaligenes, Rhodopseudomonas, Ochrobactrum, Micrococcus, Serratia, Penicillium, Aspergillus, among others, all of which have good degradation efficiency. Two main intermediates, 2-amino-4,6-dimethoxypyrimidine (ADMP) and 2-aminosulfonyl-N,N-dimethylnicotinamide (ASDM), are produced during microbial degradation and are derived from the C-N, C-S, and S-N bond breaks on the sulfonylurea bridge, covering almost every bacterial degradation pathway. In addition, enzymes related to the degradation of nicosulfuron have been identified successively, including the manganese ABC transporter (hydrolase), Flavin-containing monooxygenase (oxidase), and E3 (esterase). Further in-depth studies based on molecular biology and genetics are needed to elaborate on their role in the evolution of novel catabolic pathways and the microbial degradation of nicosulfuron. To date, few reviews have focused on the microbial degradation and degradation mechanisms of nicosulfuron. This review summarizes recent advances in nicosulfuron degradation and comprehensively discusses the potential of nicosulfuron-degrading microorganisms for bioremediating contaminated environments, providing a reference for further research development on nicosulfuron biodegradation in the future.

Environmental occurrence, toxicity concerns, and biodegradation of neonicotinoid insecticides.

Neonicotinoids (NEOs) are fourth generation pesticides, which emerged after organophosphates, pyrethroids, and carbamates and they are widely used in vegetables, fruits, cotton, rice, and other industrial crops to control insect pests. NEOs are considered ideal substitutes for highly toxic pesticides. Multiple studies have reported NEOs have harmful impacts on non-target biological targets, such as bees, aquatic animals, birds, and mammals. Thus, the remediation of neonicotinoid-sullied environments has gradually become a concern. Microbial degradation is a key natural method for eliminating neonicotinoid insecticides, as biodegradation is an effective, practical, and environmentally friendly strategy for the removal of pesticide residues. To date, several neonicotinoid-degrading strains have been isolated from the environment, including Stenotrophomonas maltophilia, Bacillus thuringiensis, Ensifer meliloti, Pseudomonas stutzeri, Variovorax boronicumulans, and Fusarium sp., and their degradation properties have been investigated. Furthermore, the metabolism and degradation pathways of neonicotinoids have been broadly detailed. Imidacloprid can form 6-chloronicotinic acid via the oxidative cleavage of guanidine residues, and it is then finally converted to non-toxic carbon dioxide. Acetamiprid can also be demethylated to remove cyanoimine (=N-CN) to form a less toxic intermediate metabolite. A few studies have discussed the neonicotinoid toxicity and microbial degradation in contaminated environments. This review is focused on providing an in-depth understanding of neonicotinoid toxicity, microbial degradation, catabolic pathways, and information related to the remediation process of NEOs. Future research directions are also proposed to provide a scientific basis for the risk assessment and removal of these pesticides.

Bioremediation potential of laccase for catalysis of glyphosate, isoproturon, lignin, and parathion: Molecular docking, dynamics, and simulation.

The present study aimed to investigate the catalytic degradation produced by laccase in the detoxification of glyphosate, isoproturon, lignin polymer, and parathion. We explored laccase-glyphosate, laccase-lignin polymer, laccase-isoproturon, and laccase-parathion using molecular docking (MD) and molecular dynamics simulation (MDS) approaches. The results suggest that laccase interacts well with glyphosate, lignin polymer, isoproturon, and parathion during biodegradation. We calculated the root mean square deviations (RMSD) of laccase-glyphosate, laccase-lignin polymer, laccase-isoproturon, and laccase-parathion as 0.24 ± 0.02, 0.59 ± 0.32, 0.43 ± 0.07, and 0.43 ± 0.06 nm, respectively. In an aqueous solution, the stability of laccase with glyphosate, lignin polymer, isoproturon, and parathion is mediated through the formation of hydrophobic interactions, hydrogen bonds, and van der Waals interactions. The presence of xenobiotic toxic compounds in the active site changed the conformation of laccase. MDS of the laccase-substrate complexes confirmed their stability during catalytic degradation. Laccase assay results confirmed that the degradation of syringol, dihydroconiferyl alcohol, guaiacol, parathion, isoproturon, and glyphosate were 100%, 99.31%, 95.69%, 60.96%, 54.51%, and 48.34% within 2 h, respectively. Taken together, we describe a novel method to understand the molecular-level biodegradation of xenobiotic compounds through laccase and its potential application in contaminant removal.

Effects of Free or Immobilized Bacterium Stenotrophomonas acidaminiphila Y4B on Glyphosate Degradation Performance and Indigenous Microbial Community Structure.

The overuse of glyphosate has resulted in serious environmental contamination. Thus, effective techniques to remove glyphosate from the environment are required. Herein, we isolated a novel strain Stenotrophomonas acidaminiphila Y4B, which completely degraded glyphosate and its major metabolite aminomethylphosphonic acid (AMPA). Y4B degraded glyphosate over a broad concentration range (50-800 mg L-1), with a degradation efficiency of over 98% within 72 h (50 mg L-1). Y4B degraded glyphosate via the AMPA pathway by cleaving the C-N bond, followed by degradation of AMPA and subsequent metabolism. Y4B demonstrated strong competitiveness and substantially accelerated the degradation of glyphosate in different soils, degrading 71.93 and 89.81% of glyphosate (400 mg kg-1) within 5 days in sterile and nonsterile soils, respectively. The immobilized cells of Y4B were more efficient than their free cells and they displayed excellent biodegradation efficiency in a sediment-water system. Taken together, Y4B is an ideal degrader for the bioremediation of glyphosate-contaminated sites.

Plasma Aß42/Aß40 and p-tau181 Predict Long-Term Clinical Progression in a Cohort with Amnestic Mild Cognitive Impairment.

BACKGROUND: Previous studies reported the value of blood-based biomarkers in predicting Alzheimer disease (AD) progression among individuals with different disease stages. However, evidence regarding the value of these markers in those with amnestic mild cognitive impairment (aMCI) is insufficient. METHODS: A cohort with 251 aMCI individuals were followed for up to 8 years. Baseline blood biomarkers were measured on a single-molecule array platform. Multipoint clinical diagnosis and domain-specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression. RESULTS: Individuals with low Aß42/Aß40 and high p-tau181 at baseline demonstrated the highest AD risk (hazard ratio = 4.83, 95% CI 2.37-9.86), and the most dramatic decline across cognitive domains. Aß42/Aß40 and p-tau181, combined with basic characteristics performed the best in predicting AD conversion (AUC = 0.825, 95% CI 0.771-0.878). CONCLUSIONS: Combining Aß42/Aß40 and p-tau181 may be a feasible indicator for AD progression in clinical practice, and a potential composite marker in clinical trials.

In-situ formable dextran/chitosan-based hydrogels functionalized with collagen and EGF for diabetic wounds healing.

Delayed or non-healing skin wounds causing gangrene or even amputation, greatly threats diabetic patients lives. Herein, a bioactive, in-situ formable hydrogel based wound dressing was designed through simple Schiff base reaction. Oxidized dextran (OD) and carboxyethyl chitosan (CEC) were crosslinked together and applied as the main porous framework of hydrogel. To improve the mechanical strength and biocompatibility, collagen (Col) and EGF (Epidermal Growth Factor) were introduced into OD-CEC precursors: (1) after addition of only Col, the mechanical strength of hydrogels was improved by participating the functional -NH2 group of Col into the crosslinking process. Moreover, swelling ratio was as high as 750% on 3%OD-3%CEC-Col (water retention rate was 65 wt% after 7 days). (2) Once we introduced both Col and EGF into the OD-CEC hydrogel, the proliferation of mouse embryonic fibroblast (NIH 3T3) cells was promoted using 3%OD-3%CEC-Col/EGF, an accelerated wound healing was observed with 86% wound closure after only 14 operative days. Hematoxylin and eosin (H&E) staining and Masson staining indicated the synergy of Col and EGF might promote new tissue's formation, well collagen distributions and thus accelerate skin regeneration, presenting great potentials in wound healing of diabetic patients.

Association Between Body Mass Index and Incident Dementia Among Community-Dwelling Older Adults: The Shanghai Aging Study.

BACKGROUND: The relationship between body mass index (BMI) and dementia is inconclusive. Undesirable loss of fat-free mass is a risk factor for cognitive decline while obesity is also a risk factor for cardio-metabolic disorders among the older adults. OBJECTIVE: This study aimed to examine the association between BMI and incident all-cause dementia among Chinese older adults using a prospective study. METHODS: Participants were 1,627 community residents aged 60 or older without dementia from the Shanghai Aging Study. Cox regression models, incorporated with restricted cubic splines, were used to explore a nonlinear association between baseline BMI and risk of all-cause dementia as measured by hazard ratio (HR) using both frequentist and Bayesian approach. RESULTS: We diagnosed 136 incident dementia cases during the mean follow-up of 5.3 years. Compared with moderate BMI (18.5-24.0 kg/m2), low BMI (< 18.5 kg/m2) were related to an increased risk of dementia with the HR as 3.38 (95% CI 1.50-7.63), while high BMI (≥24.0 kg/m2) showed a decreased risk of dementia without statistical significance (HR = 0.91, 95% CI 0.60 to 1.39). Sensitivity analysis in participants without central obesity indicated that the association was still significant with even higher HR. Bayesian approach presented the similar results. CONCLUSION: Our result indicates that low BMI may contribute to high risk of incident dementia, even in individuals without central obesity.

Changes in lifestyle, mood, and disease management among community-dwelling older adults during the COVID-19 pandemic in China.

Background: Lives of older adults have been greatly affected by the COVID-19 pandemic. Methods: A telephone survey was conducted among the older adults aged 60 and above who lived in downtown Shanghai. We compared the lifestyle, mood, and disease management of older adults before and during the COVID-19 pandemic. Results: One hundred and fifty-six older adults in Shanghai completed the survey. The proportions of older adults with adequate consumption of meat (49.4% vs. 53.1%, P = 0.0339) and eggs (73.7% vs. 77.6%, P = 0.0143) were significantly higher than before. Participants spent significantly more time on housework (median: 2.0, IQR:1.0-3.0 vs. median: 2.0, IQR:1.0-2.0 h/day; P = 0.0361) and leisure activities (median: 7.0, IQR: 5.0-8.6 vs. median: 6.0, IQR: 4.0-8.5 h/day; P<0.0001) during the pandemic than before. More participants developed new hobbies (27.6% vs. 36.5%, P = 0.0470) and learned new skills (5.1% vs. 19.9%, P<0.0001). However, the number of participants routinely self-testing blood glucose and/or blood pressure decreased from 77.6% before to 64.1% during the pandemic (P = 0.0002). Conclusions: The COVID-19 pandemic affected the lifestyle, mood, and chronic diseases management among community-dwelling older adults. Supportive measures and interventions need to be tailored to older adults living in the community.

Biofilm-mediated bioremediation is a powerful tool for the removal of environmental pollutants.

Biofilm-mediated bioremediation is an attractive approach for the elimination of environmental pollutants, because of its wide adaptability, biomass, and excellent capacity to absorb, immobilize, or degrade contaminants. Biofilms are assemblages of individual or mixed microbial cells adhering to a living or non-living surface in an aqueous environment. Biofilm-forming microorganisms have excellent survival under exposure to harsh environmental stressors, can compete for nutrients, exhibit greater tolerance to pollutants compared to free-floating planktonic cells, and provide a protective environment for cells. Biofilm communities are thus capable of sorption and metabolization of organic pollutants and heavy metals through a well-controlled expression pattern of genes governed by quorum sensing. The involvement of quorum sensing and chemotaxis in biofilms can enhance the bioremediation kinetics with the help of signaling molecules, the transfer of genetic material, and metabolites. This review provides in-depth knowledge of the process of biofilm formation in microorganisms, their regulatory mechanisms of interaction, and their importance and application as powerful bioremediation agents in the biodegradation of environmental pollutants, including hydrocarbons, pesticides, and heavy metals.

Novel pathway of acephate degradation by the microbial consortium ZQ01 and its potential for environmental bioremediation.

The microbial degradation of acephate in pure cultures has been thoroughly explored, but synergistic metabolism at the community level has rarely been investigated. Here, we report a novel microbial consortium, ZQ01, capable of effectively degrading acephate and its toxic product methamidophos, which can use acephate as a source of carbon, phosphorus and nitrogen. The degradation conditions with consortium ZQ01 were optimized using response surface methodology at a temperature of 34.1 °C, a pH of 8.9, and an inoculum size of 2.4 × 108 CFU·mL-1, with 89.5% of 200 mg L-1 acephate degradation observed within 32 h. According to the main products methamidophos, acetamide and acetic acid, a novel degradation pathway for acephate was proposed to include hydrolysis and oxidation as the main pathways of acephate degradation. Moreover, the bioaugmentation of acephate-contaminated soils with consortium ZQ01 significantly enhanced the removal rate of acephate. The results of the present work demonstrate the potential of microbial consortium ZQ01 to degrade acephate in water and soil environments, with a different and complementary acephate degradation pathway.

A synergy between dopamine and electrostatically bound bactericide in a poly (vinyl alcohol) hybrid hydrogel for treating infected wounds.

Antibacterial hydrogels have emerged as viable options for battling infections associated with impaired wound healing. It is challenging in developing antibacterial hydrogels that have sustained and stable bactericidal activity while avoiding the use of any agents that may adversely affect safety. In view of this concern, a multi-functional polyvinyl alcohol (PVA)/sodium alginate-dopamine (SA-DA) hydrogel matrix-based wound dressing embedding with bis-quaternary triphenyl-phosphonium salt (BTPP+), that would present long-term intrinsic antimicrobial properties was developed using freeze-thawing (F-T) method herein. DA endows the hydrogel with efficient bacteria capture ability and subsequently the captured bacterial pathogens were in situ killed by electrostatically bound BTPP+, and hence significantly augmented the antibacterial efficacy. Furthermore, DA, co-operating with BTPP+ could promote erythrocyte and platelet aggregation on hydrogels, which ensures hydrogels with improved hemostasis capacity. Thus, this investigation provides a feasible simple avenue for development of long-term intrinsic antimicrobial hydrogel dressings with efficient hemostasis efficacy for infected wounds.

PEGylated Bis-Quaternary Triphenyl-Phosphonium Tosylate Allows for Balanced Antibacterial Activity and Cytotoxicity.

Quaternary triphenylphosphonium compounds (TPP+) have been widely recognized as an important antimicrobial because of their fast antimicrobial speed and broad antimicrobial spectrum. However, small-molecule TPP+ compounds have the defects of toxicity, which is the key factor that limits their practical applications. Here, two mono- and one bis-quaternary phosphonium tosylate compounds with different lengths of oligo(ethylene glycol) (OEG) chains and TPP+ as the active moiety were synthesized. Bis-TPP+ have a short OEG chain coupling two TPP+ at both ends, while mono-TPP+ attaches the OEG chain at one end in one molecule. In vitro antibacterial activities were evaluated against both Gram-positive as well as Gram-negative bacteria in terms of the inhibition zone (ZOI) and minimum inhibitory concentration (MIC). To investigate the antibacterial mechanism, ß-galactosidase activity was monitored for measuring the degree of membrane permeability correlated to the abilities to disrupt the membranes of bacteria. Moreover, their structure-antibacterial activity and structure-cytotoxicity relationships were further analyzed. The results indicated that bis-TPP+ synthesized can reach the sterilization rate 90% or more against Escherichia coli and Staphylococcus aureus at MICs of 3.1 and 1.5 mg/mL, respectively, and meanwhile, the cell proliferation can reach more than 80%. This paper represents an excellent approach for development of bis-TPP+ bactericidal molecules that would achieve an optimal balance between antimicrobial activity and cytotoxicity.