Global Analysis of Quorum Sensing Targets in the Intracellular Pathogen <i>Brucella melitensis</i> 16 M

Many pathogenic bacteria use a regulatory process termed quorum sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection of, and response to, these molecules depends on transcriptional regulators belonging to the LuxR family. Such a system has been discovered in the intracellular pathogen <i>Brucella melitensis</i>, a Gram-negative bacterium responsible for brucellosis, a worldwide zoonosis that remains a serious public health concern in countries were the disease is endemic. Genes encoding two LuxR-type regulators, VjbR and BabR, have been identified in the genome of <i>B. melitensis</i> 16 M. A Δ<i>vjbR</i> mutant is highly attenuated in all experimental models of infection tested, suggesting a crucial role for QS in the virulence of <i>Brucella</i>. At present, no function has been attributed to BabR. The experiments described in this report indicate that 5% of the genes in the <i>B. melitensis</i> 16 M genome are regulated by VjbR and/or BabR, suggesting that QS is a global regulatory system in this bacterium. The overlap between BabR and VjbR targets suggest a cross-talk between these two regulators. Our results also demonstrate that VjbR and BabR regulate many genes and/or proteins involved in stress response, metabolism, and virulence, including those potentially involved in the adaptation of <i>Brucella</i> to the oxidative, pH, and nutritional stresses encountered within the host. These findings highlight the involvement of QS as a major regulatory system in <i>Brucella</i> and lead us to suggest that this regulatory system could participate in the spatial and sequential adaptation of <i>Brucella</i> strains to the host environment

Global Analysis of Quorum Sensing Targets in the Intracellular Pathogen <i>Brucella melitensis</i> 16 M

Many pathogenic bacteria use a regulatory process termed quorum sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection of, and response to, these molecules depends on transcriptional regulators belonging to the LuxR family. Such a system has been discovered in the intracellular pathogen <i>Brucella melitensis</i>, a Gram-negative bacterium responsible for brucellosis, a worldwide zoonosis that remains a serious public health concern in countries were the disease is endemic. Genes encoding two LuxR-type regulators, VjbR and BabR, have been identified in the genome of <i>B. melitensis</i> 16 M. A Δ<i>vjbR</i> mutant is highly attenuated in all experimental models of infection tested, suggesting a crucial role for QS in the virulence of <i>Brucella</i>. At present, no function has been attributed to BabR. The experiments described in this report indicate that 5% of the genes in the <i>B. melitensis</i> 16 M genome are regulated by VjbR and/or BabR, suggesting that QS is a global regulatory system in this bacterium. The overlap between BabR and VjbR targets suggest a cross-talk between these two regulators. Our results also demonstrate that VjbR and BabR regulate many genes and/or proteins involved in stress response, metabolism, and virulence, including those potentially involved in the adaptation of <i>Brucella</i> to the oxidative, pH, and nutritional stresses encountered within the host. These findings highlight the involvement of QS as a major regulatory system in <i>Brucella</i> and lead us to suggest that this regulatory system could participate in the spatial and sequential adaptation of <i>Brucella</i> strains to the host environment

Global Analysis of Quorum Sensing Targets in the Intracellular Pathogen <i>Brucella melitensis</i> 16 M

Many pathogenic bacteria use a regulatory process termed quorum sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection of, and response to, these molecules depends on transcriptional regulators belonging to the LuxR family. Such a system has been discovered in the intracellular pathogen <i>Brucella melitensis</i>, a Gram-negative bacterium responsible for brucellosis, a worldwide zoonosis that remains a serious public health concern in countries were the disease is endemic. Genes encoding two LuxR-type regulators, VjbR and BabR, have been identified in the genome of <i>B. melitensis</i> 16 M. A Δ<i>vjbR</i> mutant is highly attenuated in all experimental models of infection tested, suggesting a crucial role for QS in the virulence of <i>Brucella</i>. At present, no function has been attributed to BabR. The experiments described in this report indicate that 5% of the genes in the <i>B. melitensis</i> 16 M genome are regulated by VjbR and/or BabR, suggesting that QS is a global regulatory system in this bacterium. The overlap between BabR and VjbR targets suggest a cross-talk between these two regulators. Our results also demonstrate that VjbR and BabR regulate many genes and/or proteins involved in stress response, metabolism, and virulence, including those potentially involved in the adaptation of <i>Brucella</i> to the oxidative, pH, and nutritional stresses encountered within the host. These findings highlight the involvement of QS as a major regulatory system in <i>Brucella</i> and lead us to suggest that this regulatory system could participate in the spatial and sequential adaptation of <i>Brucella</i> strains to the host environment

Protein Kinase and HDAC Inhibitors from the Endophytic Fungus <i>Epicoccum nigrum</i>

A chemical investigation of the endophytic fungus <i>Epicoccum nigrum</i> isolated from leaves of <i>Mentha suaveolens</i> collected in Morocco resulted in the isolation of five new polyketides, epicocconigrones A and B (<b>1</b> and <b>2</b>), 3-methoxyepicoccone B (<b>3</b>), 3-methoxyepicoccone (<b>4</b>), and 2,3,4-trihydroxy-6-(methoxymethyl)-5-methylbenzaldehyde (<b>5</b>), together with five known compounds (<b>6</b>–<b>10</b>). The structures of the new compounds were unambiguously determined by extensive analysis of the 1D and 2D NMR and mass spectroscopic data. Compounds <b>1</b> and <b>10</b> showed potent inhibition of at least 15 protein kinases with IC₅₀ values ranging from 0.07 to 9.00 μM. Moreover, compounds <b>1</b> and <b>10</b> inhibited histone deacetylase (HDAC) activities with IC₅₀ values of 9.8 and 14.2 μM, respectively. A preliminary structure–activity relationship is discussed. Interestingly, compounds <b>1</b> and <b>10</b> exert mainly cytostatic effects in human lymphoma RAJI and U-937 cell lines