Author:
Jayaraman Vijay,Khan Shafqat Ali,Perinbam Kumar,Rakheja Isha,Vadakkepat Abhinav Koyamangalath,Chaudhary Santosh Kumar,Pandey Asheesh Kumar,Mitra Joydeep
Abstract
AbstractCholera toxin, encoded by thectxgene, is a key virulence factor in toxigenicVibrio cholerae(ctx+) strains. However, some non-toxigenicV. cholerae(ctx-) strains are also pathogenic to humans and the mechanism involved in low-pH tolerance and pathogenicity in these strains remains unclear. To address this, we profiled the growth and chitinase activity in different pH of two clinical isolates ofV. cholerae: VC20, actx+strain, and WO5, actx-strain. We also compared the expression level of key genes involved in pathogenesis between the strains. WO5, the non-toxigenic strain had robust growth and greater chitinase activity across a wide pH range, in comparison to VC20. Additionally, WO5 expressed higher levels of transcripts from genes implicated in host cell adhesion and virulence, namelyompKandtoxT, respectively. Notably, we propose that lowerhapRlevels in WO5 contrary to VC20 is key to its low-pH tolerance. To systematically identify genes involved in low pH tolerance, we used a sequence-based homology search and found a widespread presence of low-pH adaptation modules, lysine-cadaverine, and ornithine-putrescine in multiple representative species of theVibriophylum. Furthermore, our analysis suggests that the loss of a gene encoding nitrite reductase that confers low pH tolerance is specific toV. choleraeandV. mimicus. Together, these findings reveal that the low-pH tolerance enhances the chitinase activity of the non-toxigenic strain that could helpV. choleraeto survive the acidic environment of the stomach and readily colonize the intestine.
Publisher
Cold Spring Harbor Laboratory
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