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Cyclic di-GMP signaling and the Type IV macromolecule secretion system in Xanthomonas citri

Grant number: 11/07777-5
Support Opportunities:Research Projects - Thematic Grants
Duration: December 01, 2011 - February 28, 2018
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Shaker Chuck Farah
Grantee:Shaker Chuck Farah
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Roberto Kopke Salinas
Associated researchers:Guilherme Menegon Arantes
Associated grant(s):16/08707-4 - Multiuser equipment approved in grant 2011/07777-5: SEC-MALS (three angle laser light scattering system), AP.EMU
15/04859-1 - Structure and function of the type IV secretion system from the phytopathogen Xanthomonas citri by nuclear magnetic resonance in solution, AV.EXT
13/50355-0 - Structure and dynamics of proteins by high-resolution NMR spectroscopy, SAXS, and computation, AP.R
13/50362-6 - Structural relationships of the flavonoid apigenin and hnRNPA2 define the role of plant phytochemicals in the regulation of alternative splicing, AP.R
Associated scholarship(s):15/25381-2 - Study of the role of type IV secretion system of Xanthomonas citri and Stenotrophomonas maltophilia in the interaction with Dictyostelium discoideum., BP.PD
15/13318-4 - Structural engineering of the active site of diguanylate cyclase (GGDEF) domains to produce new second messengers, BP.DD
15/17073-6 - Regulation of Xanthomonas citri Type IV pilus, BP.PD
11/22571-4 - Regulation of Xanthomonas citri Type IV pilus, BP.PD


In this Project we propose to develop two lines of research into the biology of the phytopathogen Xanthomonas citri (Xac), the causative agent of citrus canker. i) Metabolism of the second messenger c-di-GMP: synthesis, degradation and receptors. Bacteria can adopt multiple lifestyles. At one extreme, individual cells can undergo planktonic growth in liquid medium in which they use flagella to swim in the direction of chemo-attractants or away from chemo-repellents. At the other extreme, another lifestyle involves growth on a surface as part of a static community, often called a biofilm. The ability to switch between these and intermediate lifestyles requires the coordination of a series of developmental events and complex physiological behaviors such as quorum sensing, several types of motility, adhesion to surfaces, secretion of exopolysaccharides, surfactants and extracellular enzymes and the production of virulence factors. There is a wealth of evidence that the dinucleotide bis(3´à5´) cyclic di-GMP (c-di-GMP) plays a central role in these processes in bacteria. C-di-GMP is synthesized by diguanylate cyclases (GGDEF domains), degraded by two classes of phosphodiesterases (EAL and HD-GYP domains), and many different c-di-GMP receptor families have been characterized (PilZ, FleQ, CLP, non-catalystic GGDEF and EAL domains as well as riboswitches). The phytopathogen Xanthomonas citri (Xac), that causes citrus canker, will be used as a model to study the complexity of c-di-GMP mediated bacterial signaling networks. The Xac genome codes for several dozen potential cyclases, phosphodiesterases and c-di-GMP receptors, the majority of which are covalently or non-covalently associated with other protein domains involved in a large variety of molecular signaling activities. Our long-term challenge is to understand the structure-function relationships that control cyclase and phosphodiesterase enzymatic activity as well as the principles that regulate receptor affinity for this second messenger. We are also interested in understanding the variety of interactions that these domains undergo with other domain families and how these interactions modulate cyclase and phosphodiesterase activities and receptor affinities. ii) Type IV secretion systems. Many pathogenic bacteria use macromolecular secretion systems to transfer virulence factors into host cells. In this project we plan to continue our studies into the structure and function of the Xac Type IV secretion system (T4SS). Its large size (multiple copies of at least a dozen different subunits and a molecular mass of > 1 megaDalton) creates significant challenges for structural studies. Another major challenge is to identify and characterize specific substrates secreted by this system. In our studies, we propose to employ a variety of experimental methods including X-ray crystallography, nuclear magnetic resonance (NMR), SAXS, molecular dynamics simulations, statistical coupling analysis (SCA), the production and characterization of gene knock-outs, enzymology and gene expression studies (AU)

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Scientific publications (14)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CENENS, WILLIAM; ANDRADE, MAXUEL O.; LLONTOP, EDGAR; ALVAREZ-MARTINEZ, CRISTINA E.; SGRO, GERMAN G.; FARAH, CHUCK S.. Bactericidal type IV secretion system homeostasis in Xanthomonas citri. PLOS PATHOGENS, v. 16, n. 5, . (19/12234-2, 15/18237-2, 14/04294-1, 17/17303-7, 11/07777-5)
BAYER-SANTOS, ETHEL; CENENS, WILLIAM; MATSUYAMA, BRUNO YASUI; OKA, GABRIEL UMAJI; DI SESSA, GIANCARLO; MININEL, IZABEL DEL VALLE; ALVES, TIAGO LUBIANA; FARAH, CHUCK SHAKER. The opportunistic pathogen Stenotrophomonas maltophilia utilizes a type IV secretion system for interbacterial killing. PLOS PATHOGENS, v. 15, n. 9, . (15/25381-2, 17/17303-7, 18/04553-8, 15/18237-2, 17/02178-2, 16/00458-5, 11/07777-5)
OLIVEIRA, LUCIANA COUTINHO; SOUZA, DIORGE PAULO; OKA, GABRIEL UMAJI; LIMA, FILIPE DA SILVA; OLIVEIRA, RONALDO JUNIO; FAVARO, DENIZE CRISTINA; WIENK, HANS; BOELENS, ROLF; FARAH, CHUCK SHAKER; SALINAS, ROBERTO KOPKE. VirB7 and VirB9 Interactions Are Required for the Assembly and Antibacterial Activity of a Type IV Secretion System. Structure, v. 24, n. 10, p. 1707-1718, . (13/17883-2, 11/07777-5)
GUZZO, CRISTIANE R.; DUNGER, GERMAN; SALINAS, ROBERTO KOPKE; FARAH, CHUCK S.. Structure of the PilZ-FimX(EAL)-c-di-GMP Complex Responsible for the Regulation of Bacterial Type IV Pilus Biogenesis. Journal of Molecular Biology, v. 425, n. 12, p. 2174-2197, . (11/07777-5, 11/22571-4, 09/14477-8)
SGRO, GERMAN G.; COSTA, TIAGO R. D.; CENENS, WILLIAM; SOUZA, DIORGE P.; CASSAGO, ALEXANDRE; DE OLIVEIRA, LUCIANA COUTINHO; SALINAS, ROBERTO K.; PORTUGAL, V, RODRIGO; FARAH, CHUCK S.; WAKSMAN, GABRIEL. Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri. NATURE MICROBIOLOGY, v. 3, n. 12, p. 1429-1440, . (17/17303-7, 11/07777-5)
ABIKO, LAYARA AKEMI; VITALE, PHELIPE M.; FAVARO, DENIZE C.; HAUK, PRICILA; LI, DA-WEI; YUAN, JIAQI; BRUSCHWEILER-LI, LEI; SALINAS, ROBERTO K.; BRUSCHWEILER, RAFAEL. Model for the allosteric regulation of the Na+/Ca2+ exchanger NCX. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, v. 84, n. 5, p. 580-590, . (13/50355-0, 13/17883-2, 11/07777-5)
DUNGER, GERMAN; LLONTOP, EDGAR; GUZZO, CRISTIANE R.; FARAH, CHUCK S.. The Xanthomonas type IV pilus. Current Opinion in Microbiology, v. 30, p. 88-97, . (11/07777-5)
DUNGER, GERMAN; GUZZO, CRISTIANE R.; ANDRADE, MAXUEL O.; JONES, JEFFREY B.; FARAH, CHUCK S.. Xanthomonas citri subsp citri Type IV Pilus Is Required for Twitching Motility, Biofilm Development, and Adherence. MOLECULAR PLANT-MICROBE INTERACTIONS, v. 27, n. 10, p. 1132-1147, . (11/07777-5, 11/22571-4)
OLIVEIRA, MAYCON C.; TEIXEIRA, RAPHAEL D.; ANDRADE, MAXUEL O.; PINHEIRO, GLAUCIA M. S.; RAMOS, CARLOS H. I.; FARAH, CHUCK S.. Cooperative Substrate Binding by a Diguanylate Cyclase. Journal of Molecular Biology, v. 427, n. 2, p. 415-432, . (11/07777-5)
TEIXEIRA, RAPHAEL D.; GUZZO, CRISTIANE R.; AREVALO, SANTIAGO JUSTO; ANDRADE, MAXUEL O.; ABRAHAO, JOSIELLE; DE SOUZA, ROBSON F.; FARAH, CHUCK S.. A bipartite periplasmic receptor-diguanylate cyclase pair (XAC2383-XAC2382) in the bacterium Xanthomonas citri. Journal of Biological Chemistry, v. 293, n. 27, p. 10767-10781, . (11/07777-5)
BAYER-SANTOS, ETHEL; LIMA, LIDIA DOS PASSOS; CESETI, LUCAS DE MORAES; RATAGAMI, CAMILA YURI; DE SANTANA, ELIANE SILVA; DA SILVA, ALINE MARIA; FARAH, CHUCK SHAKER; ALVAREZ-MARTINEZ, CRISTINA ELISA. Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF sigma factor and cognate Ser/Thr kinase. ENVIRONMENTAL MICROBIOLOGY, v. 20, n. 4, SI, p. 1562-1575, . (16/08400-6, 14/19720-6, 14/25261-4, 11/07777-5, 15/25381-2)
CESETI, LUCAS M.; DE SANTANA, ELIANE S.; RATAGAMI, CAMILA Y.; BARREIROS, YASMIN; LIMA, LIDIA DOS PASSOS; DUNGER, GERMAN; FARAH, CHUCK S.; ALVAREZ-MARTINEZ, CRISTINA E.. The Xanthomonas citri pv. citri Type VI Secretion System is Induced During Epiphytic Colonization of Citrus. Current Microbiology, v. 76, n. 10, p. 1105-1111, . (11/22571-4, 16/08400-6, 14/19720-6, 17/02318-9, 18/01852-4, 14/25261-4, 11/07777-5)
BAYER-SANTOS, ETHEL; LIMA, LIDIA DOS PASSOS; CESETI, LUCAS DE MORAES; RATAGAMI, CAMILA YURI; DE SANTANA, ELIANE SILVA; DA SILVA, ALINE MARIA; FARAH, CHUCK SHAKER; ALVAREZ-MARTINEZ, CRISTINA ELISA. Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF sigma factor and cognate Ser/Thr kinase. ENVIRONMENTAL MICROBIOLOGY, v. 20, n. 4, p. 14-pg., . (15/25381-2, 16/08400-6, 11/07777-5, 14/19720-6, 14/25261-4)

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