RESUMO
AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.
Assuntos
Escherichia coli/genética , Transferência Genética Horizontal/efeitos dos fármacos , Ácido Linoleico/farmacologia , Ácido alfa-Linolênico/farmacologia , Adenosina Trifosfatases/química , Adenosina Trifosfatases/genética , Colistina/farmacologia , Conjugação Genética , Farmacorresistência Bacteriana , Escherichia coli/classificação , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Expressão Gênica/efeitos dos fármacos , Ácido Linoleico/química , Ácido Linoleico/metabolismo , Simulação de Acoplamento Molecular , Plasmídeos/genética , Ácido alfa-Linolênico/química , Ácido alfa-Linolênico/metabolismoRESUMO
OBJECTIVE: The purpose of this study was to uncover the potential impact of alcohol consumption on the tumorigenesis of colorectal cancer (CRC) and the underlying mechanism. PATIENTS AND METHODS: Overall survival was compared in CRC patients either with alcohol consumption or not. Subsequently, a mouse model of CRC was established by azoxymethane (AOM) administration. Tumor number and size were compared in CRC mice fed with Lieber-DeCarli liquid diet or normal diet. At last, pathological differences in cell proliferation, apoptosis, inflammation, and intestinal permeability, in intestines harvested from CRC mice fed with Lieber-DeCarli liquid diet or normal diet were assessed. RESULTS: It was found that the prognosis was worse in CRC patients with alcohol consumption. In CRC mice fed with Lieber-DeCarli liquid diet, more tumor tissues were found than those in the controls. Besides, alcohol consumption remarkably impaired intestinal permeability, making it easier for bacteria to invade epithelial cells. Moreover, oral gavage of probiotics markedly improved intestinal permeability and reduced tumor number in CRC mice fed with Lieber-DeCarli liquid diet. CONCLUSIONS: Probiotics can inhibit the development of alcohol-induced CRC by protecting intestinal permeability.