Subtle Changes Due to Mutations in the GGDEF Domain Result in Loss of Biofilm Forming Activity in the VC0395_0300 Protein from Vibrio cholerae, but No Major Change in the Overall Structure

Chouhan, Om Prakash; Biswas, Sumit

doi:10.2174/0929866525666180628162405

Cited by 3 publications

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“…A DGC with a GGEEF domain was reported by our group in 2017 (Bandekar et al, 2017;Chouhan and Biswas, 2018). While VC0395_0300 was shown to synthesize c-di-GMP actively and had an essential role to play in the biofilm formation of V. cholerae, mutations at the central positions of the GGEEF sequence were detrimental to the functional activity of the protein (Chouhan et al, 2016).…”

Section: Vc0395_0300mentioning

confidence: 97%

Diguanylate Cyclases in Vibrio cholerae: Essential Regulators of Lifestyle Switching

Biswas

Chouhan

Bandekar

2020

Front. Cell. Infect. Microbiol.

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Biofilm formation in Vibrio cholerae empowers the bacteria to lead a dual lifestyle and enhances its infectivity. While the formation and dispersal of the biofilm involves multiple components-both proteinaceous and non-proteinaceous, the key to the regulatory control lies with the ubiquitous secondary signaling molecule, cyclic-di-GMP (c-di-GMP). A number of different cellular components may interact with c-di-GMP, but the onus of synthesis of this molecule lies with a class of enzymes known as diguanylate cyclases (DGCs). DGC activity is generally associated with proteins possessing a GGDEF domain, ubiquitously present across all bacterial systems. V. cholerae is also endowed with multiple DGCs and information about some of them have been pouring in over the past decade. This review summarizes the DGCs confirmed till date in V. cholerae, and emphasizes the importance of DGCs and their product, c-di-GMP in the virulence and lifecycle of the bacteria.

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Section: Vc0395_0300mentioning

confidence: 97%

Diguanylate Cyclases in Vibrio cholerae: Essential Regulators of Lifestyle Switching

Biswas

Chouhan

Bandekar

2020

Front. Cell. Infect. Microbiol.

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“…Thus, it is not clear if the phenotype of the BB3576-GGAAF mutant protein is due to loss of DGC activity or destabilization of the protein. It is important to note that similar mutations have been made in many DGCs with no apparent loss of protein stability (14)(15)(16). Moreover, only when intracellular c-di-GMP levels were high was motility reduced in the soft agar assay (Fig.…”

Section: Resultsmentioning

confidence: 60%

Bordetella bronchiseptica Diguanylate Cyclase BdcA Regulates Motility and Is Important for the Establishment of Respiratory Infection in Mice

et al. 2019

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Bacteria can be motile and planktonic or, alternatively, sessile and participating in the biofilm mode of growth. The transition between these lifestyles can be regulated by a second messenger, cyclic dimeric GMP (c-di-GMP). High intracellular c-di-GMP concentration correlates with biofilm formation and motility inhibition in most bacteria, including Bordetella bronchiseptica, which causes respiratory tract infections in mammals and forms biofilms in infected mice. We previously described the diguanylate cyclase BdcA as involved in c-di-GMP synthesis and motility regulation in B. bronchiseptica; here, we further describe the mechanism whereby BdcA is able to regulate motility and biofilm formation. Amino acid replacement of GGDEF with GGAAF in BdcA is consistent with the conclusion that diguanylate cyclase activity is necessary for biofilm formation and motility regulation, although we were unable to confirm the stability of the mutant protein. In the absence of the bdcA gene, B. bronchiseptica showed enhanced motility, strengthening the hypothesis that BdcA regulates motility in B. bronchiseptica. We showed that c-di-GMP-mediated motility inhibition involved regulation of flagellin expression, as high c-di-GMP levels achieved by expressing BdcA significantly reduced the level of flagellin protein. We also demonstrated that protein BB2109 is necessary for BdcA activity, motility inhibition, and biofilm formation. Finally, absence of the bdcA gene affected bacterial infection, implicating BdcA-regulated functions as important for bacterium-host interactions. This work supports the role of c-di-GMP in biofilm formation and motility regulation in B. bronchiseptica, as well as its impact on pathogenesis. IMPORTANCE Pathogenesis of Bordetella spp., like that of a number of other pathogens, involves biofilm formation. Biofilms increase tolerance to biotic and abiotic factors and are proposed as reservoirs of microbes for transmission to other organs (trachea, lungs) or other hosts. Bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is a second messenger that regulates transition between biofilm and planktonic lifestyles. In Bordetella bronchiseptica, high c-di-GMP levels inhibit motility and favor biofilm formation. In the present work, we characterized a B. bronchiseptica diguanylate cyclase, BdcA, which regulates motility and biofilm formation and affects the ability of B. bronchiseptica to colonize the murine respiratory tract. These results provide us with a better understanding of how B. bronchiseptica can infect a host.

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Structure of the active GGEEF domain of a diguanylate cyclase from Vibrio cholerae

Chouhan

Roske

Heinemann

et al. 2020

Biochemical and Biophysical Research Communications

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Subtle Changes Due to Mutations in the GGDEF Domain Result in Loss of Biofilm Forming Activity in the VC0395_0300 Protein from Vibrio cholerae, but No Major Change in the Overall Structure

Abstract: This led us to conclude that whatever changes that occur in the mutated proteins, do not disturb the GGEEF domain architecture, but are restricted to the local architecture, and are hence, subtle in nature.

Cited by 3 publications

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Diguanylate Cyclases in Vibrio cholerae: Essential Regulators of Lifestyle Switching

Diguanylate Cyclases in Vibrio cholerae: Essential Regulators of Lifestyle Switching

Bordetella bronchiseptica Diguanylate Cyclase BdcA Regulates Motility and Is Important for the Establishment of Respiratory Infection in Mice

Structure of the active GGEEF domain of a diguanylate cyclase from Vibrio cholerae

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