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      3-methylcrotonyl Coenzyme A (CoA) carboxylase complex is involved in the Xanthomonas citri subsp. citri lifestyle during citrus infection

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          Abstract

          Citrus canker is a disease caused by the phytopathogen Xanthomonas citri subsp. citri (Xcc), bacterium which is unable to survive out of the host for extended periods of time. Once established inside the plant, the pathogen must compete for resources and evade the defenses of the host cell. However, a number of aspects of Xcc metabolic and nutritional state, during the epiphytic stage and at different phases of infection, are poorly characterized. The 3-methylcrotonyl-CoA carboxylase complex (MCC) is an essential enzyme for the catabolism of the branched-chain amino acid leucine, which prevents the accumulation of toxic intermediaries, facilitates the generation of branched chain fatty acids and/or provides energy to the cell. The MCC complexes belong to a group of acyl-CoA carboxylases (ACCase) enzymes dependent of biotin. In this work, we have identified two ORFs (XAC0263 and XAC0264) encoding for the α and β subunits of an acyl-CoA carboxylase complex from Xanthomonas and demonstrated that this enzyme has MCC activity both in vitro and in vivo. We also found that this MCC complex is conserved in a group of pathogenic gram negative bacteria. The generation and analysis of an Xcc mutant strain deficient in MCC showed less canker lesions in the interaction with the host plant, suggesting that the expression of these proteins is necessary for Xcc fitness during infection.

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          Regulation and secretion of Xanthomonas virulence factors.

          Plant pathogenic bacteria of the genus Xanthomonas cause a variety of diseases in economically important monocotyledonous and dicotyledonous crop plants worldwide. Successful infection and bacterial multiplication in the host tissue often depend on the virulence factors secreted including adhesins, polysaccharides, LPS and degradative enzymes. One of the key pathogenicity factors is the type III secretion system, which injects effector proteins into the host cell cytosol to manipulate plant cellular processes such as basal defense to the benefit of the pathogen. The coordinated expression of bacterial virulence factors is orchestrated by quorum-sensing pathways, multiple two-component systems and transcriptional regulators such as Clp, Zur, FhrR, HrpX and HpaR. Furthermore, virulence gene expression is post-transcriptionally controlled by the RNA-binding protein RsmA. In this review, we summarize the current knowledge on the infection strategies and regulatory networks controlling secreted virulence factors from Xanthomonas species.
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            Fatty acid synthesis and its regulation.

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              Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery.

              L. Tong (2005)
              Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in most living organisms. Mice deficient in ACC2 have continuous fatty acid oxidation and reduced body fat and body weight, validating this enzyme as a target for drug development against obesity, diabetes and other symptoms of the metabolic syndrome. ACC is a biotin-dependent enzyme and catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in most eukaryotes. The activity of the enzyme can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. This review will summarize the structural information that is now available for both the BC and CT enzymes, as well as the molecular mechanism of action of potent ACC inhibitors. The current intense research on these enzymes could lead to the development of novel therapies against metabolic syndrome and other diseases.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: SoftwareRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 June 2018
                2018
                : 13
                : 6
                : e0198414
                Affiliations
                [001]Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
                Fujian Agriculture and Forestry University, CHINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-3339-0100
                Article
                PONE-D-18-01626
                10.1371/journal.pone.0198414
                5991677
                29879157
                c5bccfca-6a53-4d19-87e3-1ddea5117190
                © 2018 Tomassetti et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 January 2018
                : 19 May 2018
                Page count
                Figures: 8, Tables: 2, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003074, Agencia Nacional de Promoción Científica y Tecnológica;
                Award ID: P. BID - PICT 2014-1454
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003074, Agencia Nacional de Promoción Científica y Tecnológica;
                Award ID: P. BID - PICT 2013-0625
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002923, Consejo Nacional de Investigaciones Científicas y Técnicas;
                Award ID: PIP-2014-0764
                Award Recipient :
                BSG, NG, JO, HG, and LD are staff members and CVV postdoctoral fellow of the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET). This work was supported by Agencia Nacional de Promoción Científica y Tecnológica (P. BID PICT 2014-1454 to LD, PICT 2013-0625 to JO), CONICET (PIP-2014-0764 to LD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Plant Science
                Plant Anatomy
                Leaves
                Biology and Life Sciences
                Plant Science
                Plant Pathology
                Plant Pathogens
                Plant Bacterial Pathogens
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Amino Acids
                Aliphatic Amino Acids
                Leucine
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Amino Acids
                Aliphatic Amino Acids
                Leucine
                Biology and Life Sciences
                Biochemistry
                Proteins
                Amino Acids
                Aliphatic Amino Acids
                Leucine
                Biology and Life Sciences
                Organisms
                Bacteria
                Xanthomonas
                Physical Sciences
                Chemistry
                Chemical Compounds
                Organic Compounds
                Vitamins
                B Vitamins
                Biotin
                Physical Sciences
                Chemistry
                Organic Chemistry
                Organic Compounds
                Vitamins
                B Vitamins
                Biotin
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Catabolism
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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