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Transcriptional network controlled by Candida albicans treated by a gemini quaternary ammonium compound, 1, 5-bis(dodecyl)-1, 1, 3, 5, 5-pentamethyl-3-aza-1, 5-pentanediammonium ditetrafluoroborate (PMT12-BF4)

ABSTRACT: Transcriptional network controlled by Candida albicans treated by a gemini quaternary ammonium compound, 1, 5-bis(dodecyl)-1, 1, 3, 5, 5-pentamethyl-3-aza-1, 5-pentanediammonium ditetrafluoroborate (PMT12-BF4)

PROVIDER: PRJNA530417 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8836066_1.fastq.gz	Fastqsanger.gz
	SRR8836066_2.fastq.gz	Fastqsanger.gz
	SRR8836067_1.fastq.gz	Fastqsanger.gz
	SRR8836067_2.fastq.gz	Fastqsanger.gz

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Transcriptional network controlled by Candida albicans treated by a gemini quaternary ammonium compound, 1, 5-bis(dodecyl)-1, 1, 3, 5, 5-pentamethyl-3-aza-1, 5-pentanediammonium ditetrafluoroborate (PMT12-BF4)

Project description:In order to identify genes regulated by PMT12-BF4, we compared the genome-wide expression profile in wild-type strain SC5314 untreated or treated with PMT12-BF4 via RNA sequencing. Results showed that in C. albicans 69 genes were up-regulated and 30 genes were down-regulated in the presence of PMT12-BF4. Up-regulated genes were mostly involved in iron ion-related functions (e.g. RBT5, CFL5, CFL4, FET34, FET31 etc.), and down-regulated genes were largely involved in oxidoreductase activity, vitamin binding and coenzyme binding.

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Synthesis and Antimicrobial Evaluation of Bis-morpholine Triazine Quaternary Ammonium Salts.

Project description:Efficient, environmentally and economically sustainable, and nontoxic antibacterial products are of global relevance in the fight against microorganism contamination. In this work, an easy and straightforward method for the synthesis of bis-morpholino triazine quaternary ammonium salts (bis-mTQAS) is reported, starting from 2,4,6-trichloro-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine and various N-alkylmorpholines. Bis-mTQAS were tested as antimicrobials against Gram-negative and Gram-positive bacterial strains. The best-performing bis-mTQAS were found to achieve total disinfection against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 at 50 and 400 μg/mL, respectively. Distinctively, bis-mTQAS with the highest antimicrobial efficiency had lowest cytotoxicity.

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Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure.

Project description:Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic.Main findingsThis study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.

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Project description:Combination therapies targeting malignancies aim to increase treatment efficacy and reduce toxicity. Hypomethylating drug 5-Aza-2’-deoxycytidine (5-Aza-2’) enhances transcription of tumor suppressor genes and induces replication errors via entrapment of DNMT1. Post-translational modification by SUMO plays major roles in the DNA damage response and is required for degradation of entrapped DNMT1. Here, we combine SUMOylation inhibitor TAK981 and DNA-hypomethylating agent 5-Aza-2’ to improve treatment of MYC driven hematopoietic malignancies, since MYC overexpressing tumors are sensitive to SUMOylation inhibition. We studied the classical MYC driven malignancy Burkitt lymphoma, as well as diffuse large B-cell lymphoma (DLBCL) with and without MYC translocation. SUMO inhibition prolonged the entrapment of DNMT1 to DNA, resulting in DNA damage. An increase in DNA damage was observed in cells co-treated with TAK981 and 5-Aza-2’. Both drugs synergized to reduce cell proliferation in vitro in a B cell lymphoma cell panel, including Burkitt lymphoma and DLBCL. In vivo experiments combining TAK981 (25 mg/kg) and 5-Aza-2’ (2.5 mg/kg) showed a significant reduction in outgrowth of Burkitt lymphoma in an orthotopic xenograft model. In contrast, single dosing of TAK981 was ineffective and single dosing of 5-Aza-2’ only led to a modest outgrowth reduction. TAK981 and 5-Aza-2’ synergize to reduce B cell Lymphoma outgrowth in vitro and in vivo. SUMOylation is a key-player in the repair of DNA damage, hence upon TAK981 treatment the repair of DNA damage induced by 5-Aza-2’ treatment is impaired. Our results demonstrate the potential of tailored combination of drugs, based on insight in molecular mechanisms, to improve the efficacy of cancer therapies.

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Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide.

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