Investigation of ascorbic acid (vitamin C) fermentation in the human pathogen Vibrio cholerae
Date
2020
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Ascorbic acid, commonly known as vitamin C, is a ubiquitous 6-carbon carbohydrate characterized by its ability to scavenge free radicals. In enteric bacteria such as Escherichia coli, L-ascorbate can be utilized as a primary nutrient and the Ula system (consisting of the operon ulaABCDEF and divergently transcribed genes ulaG and ulaR) is required for L-ascorbate fermentation. In this study, we identified homologs of the Ula system within Vibrio species and showed that Vibrio cholerae and V. vulnificus were able to utilize L-ascorbate as a carbon and energy source. Growth pattern assays of a V. cholerae ulaG in-frame deletion mutant, which encodes a lactonase, demonstrated it is essential for L-ascorbate fermentation. Expression analysis demonstrated that the V. cholerae Ula catabolism and transport genes were significantly upregulated in the presence of L-ascorbate or mouse intestinal mucus compared to growth on glucose. Also, in in vitro growth competition assays in intestinal mucus between wild type and the ulaG mutant showed the mutant was outcompeted by wild type. Within the ula operon in V. cholerae, ORF VCA0243 showed homology to a pyridoxal phosphate (PLP) phosphatase, an enzyme that converts the active form of vitamin B6 pyridoxal-5-P to its inactive form, pyridoxal (PL). An in-frame deletion mutant of VCA0243 resulted in a growth defect with L-ascorbate as a carbon and energy source. In addition, deletion of VCA0243 resulted in significant changes in carbon and amino acid utilization; suggesting a larger role of this gene in central metabolism. The ability to efficiently and effectively scavenge for nutrients provides competitive advantages for pathogens when colonizing the human intestines. The genes required for the fermentation of L-ascorbate have a limited distribution within the family Vibrionaceae, but are present in all members of the Cholerae clade, several members of which are pathogens of humans. The ability of V. cholerae to utilize L-ascorbate can potentially increase the competitiveness of this deadly pathogen during colonization and infection.
Description
Keywords
Ascorbic acid, Vitamin C, Vibrio cholerae