Itaconic acid inhibits growth of a pathogenic marine Vibrio strain: A metabolomics approach

Abstract

The antimicrobial role of itaconic acid (ITA) has been recently discovered in mammalian cells. In our previous studies, we discovered that marine molluscs biosynthesise substantial quantities of ITA when exposed to marine pathogens, but its antimicrobial function to Vibrio bacteria is currently unknown. Thus, in this study, we used an untargeted gas chromatography–mass spectrometry (GC-MS) platform to identify metabolic changes of Vibrio sp. DO1 ( V . corallyliticus / neptunius -like isolate) caused by ITA exposure. Vibrio sp. DO1 was cultured in Luria-Bertani broth supplemented with 3 mM sodium acetate and with different concentrations of ITA (0, 3 and 6 mM) for 24 h. The results showed that ITA completely inhibited Vibrio sp. growth at 6 mM and partially inhibited the bacterial growth at 3 mM. A principal component analysis (PCA) revealed a clear separation between metabolite profiles of Vibrio sp. DO1 in the 3 mM ITA treatment and the control, which were different in 25 metabolites. Among the altered metabolites, the accumulation of glyoxylic acid and other metabolites in glyoxylate cycle (cis-aconitic acid, isocitric acid and fumaric acid) together with the increase of isocitrate lyase (ICL) activity in the 3 mM ITA treatment compared to the control suggest that ITA inhibited Vibrio sp. growth via disruption of central carbon metabolism.

Potential correlation between carbohydrate‐active enzyme family 48 expressed by gut microbiota and the expression of intestinal epithelial AMP‐activated protein kinase β

“…For example, RM-fed mice displayed a relatively high abundance of Chlamydiaceae, Lachnospiraceae, and Erysipelotrichaceae at the family level, when compared with other experimental groups (Chen et al, 2017; Radomski, Franzke, Matthiesen, Karger, & Knittler, 2019). Additionally, members of the Lachnospiraceae and Erysipelotrichaceae families have previously been suggested to be associated with microbe TMA generation and development of atherosclerosis (Qiu, Tao, Xiong, Yu, & Wei, 2018).The clear separation in the species distribution and abundance in the gut microbiota of the RM-fed group as defined by the PCA profiles supported the finding that the RM diet had a significant impact on the composition of gut microbiota(Figure 2b;Nguyen et al, 2019).The composition of the gut microbiota at the phylum and genus levels induced by the experimental diets is shown inFigure 3. These results(Figure 3a)suggest that intake of red meat promoted the growth of members of the Firmicutes phylum, while reducing the relative abundance of the Bacteroidetes phylum.…”

Effect of pH on the antimicrobial activity of the macrophage metabolite itaconate

“…Within activated murine macrophages, the overall concentration of itaconate has been estimated to 3-8 mM [1,2], whereas this value is only 60 µM for activated human macrophages [2]. In contrast, reported minimum inhibitory concentrations (MICs) for itaconate in bacteria range from 1 to 75 mM [2,13,15,17,[22][23][24][25]. From these numbers, whether the itaconate concentration in macrophages is high enough to effectively inhibit microbial growth has been questioned [26].…”

The Biotechnological Potential of Secondary Metabolites from Marine Bacteria

“…With regard to marine bacteria and their secondary metabolites, the targeted control of biosynthesis mechanisms by using the metabolic engineering methods to create hybrid peptides or obtain hybrid peptide synthetases by disrupting the target gene of non-ribosomal synthesis is now one of the noteworthy trends in modern biotechnology. This pathway becomes not only one of the most promising approaches to the development of novel antibiotics, but also a potential target for controlling the exocrine activity of pathogenic bacteria and, consequently, their viability [5,[93][94][95].…”