Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in Vibrio vulnificus

Abstract

The second messenger c-di-GMP is a key regulator of bacterial physiology. The V. vulnificus genome encodes nearly 100 proteins predicted to make, break, and bind c-di-GMP. However, relatively little is known regarding the environmental signals that regulate c-di-GMP levels and biofilm formation in V. vulnificus. Here, we identify calcium as a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers brp-mediated biofilm formation. We show that PAPS, a metabolic intermediate of the sulfate assimilation pathway, acts as a second messenger linking environmental calcium and sulfur source availability to the production of another intracellular second messenger (c-di-GMP) to regulate biofilm and rugose colony formation, developmental pathways that are associated with environmental persistence and efficient bivalve colonization by this potent human pathogen.

Para-Aminobenzoic Acid, Calcium, and c-di-GMP Induce Formation of Cohesive, Syp-Polysaccharide-Dependent Biofilms in Vibrio fischeri

“…Calcium directly interacts with proteins, such as the pilus-biogenesis factor PilY1 in P. aeruginosa , which enables pilus protraction and retraction; its interactions with type I pili promote E. coli to initiate entry into host cells ( 35 , 36 ). In V. vulnificus , calcium (10 mM) increases the levels of c-di-GMP, which then triggers production of the brp polysaccharide by upregulating transcription of the brp locus ( 37 ). The same amount of calcium failed to exert a big effect on c-di-GMP levels (or syp transcription) under the conditions assayed here.…”

Transcriptomic Analysis Reveals That Municipal Wastewater Effluent Enhances Vibrio vulnificus Growth and Virulence Potential

“…Calcium concentrations have been shown to influence biofilm formation by V. vulnificus and other non-cholera vibrios (Park et al, 2015;Marsden et al, 2017). It has been proposed that calcium acts as a primary environmental signal by upregulating the sulfate assimilation genes cysDN and cysC, resulting in the accumulation of 3′-phosphoadenosine 5′-phosphosulfate (PAPS; Chodur et al, 2018). The accumulation of PAPS, in FIGURE 3 | Graphical summary of altered Vibrio vulnificus gene expression or pathways with exposure to wastewater effluent.…”

Wolf in Sheep’s Clothing: Clostridioides difficile Biofilm as a Reservoir for Recurrent Infections

“…Biofilm formation can be controlled by stress response regulators that are activated by different stresses present in the host such as nutrient limitation, iron deprivation, sub-inhibitory concentrations of antibiotics, and osmotic stress [ 109 , 110 , 111 ]. Specific environmental conditions such as calcium concentration can increase the second messenger c-di-GMP concentrations that could trigger biofilm formation [ 112 ]. In some cases, biofilm formation is dependent on the nutritional conditions that will trigger metabolic adaptation and thus stimulate biofilm formation [ 106 ].…”