Regulon controlled by the GppX hybrid two component system in Porphyromonas gingivalis

The periodontal pathogen Porphyromonas gingivalis experiences a number of environmental conditions in the oral cavity, and must monitor and respond to a variety of environmental cues. However, the organism possesses only five full two‐component systems, one of which is the hybrid system GppX. To investigate the regulon controlled by GppX we performed RNA‐Seq on a ΔGppX mutant. Fifty‐three genes were upregulated and 37 genes were downregulated in the ΔGppX mutant. Pathway analyses revealed no systemic function for GppX under nutrient‐replete conditions; however, over 40% of the differentially abundant genes were annotated as encoding hypothetical proteins indicating a novel role for GppX. Abundance of small RNA was, in general, not affected by the absence of GppX. To further define the role of GppX with respect to regulation of a hypothetical protein observed with the greatest significant relative abundance change relative to a wild‐type control, PGN_0151, we constructed a series of strains in which the ΔgppX mutation was complemented with a GppX protein containing specific domain and phosphotransfer mutations. The transmembrane domains, the DNA‐binding domain and the phosphotransfer residues were all required for regulation of PGN_0151. In addition, binding of GppX to the PGN_0151 promoter regions was confirmed by an electrophoretic mobility shift assay. Both the ΔGppX mutant and a ΔPGN_0151 mutant were deficient in monospecies biofilm formation, suggesting a role for the GppX‐PGN_0151 regulon in colonization and survival of the organism.     

Stoffwechsel

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Relationship between viral load in blood, cerebrospinal fluid, brain tissue and isolated microglia with neurological disease in macaques infected with different strains of SIV

The role of the viral burden in the brain for the pathogenesis of human immunodeficiency virus-associated neurological disorders is still unclear. To address this issue, we have quantified the viral load in plasma, cerebrospinal fluid (CSF) and brain tissue of macaques infected with simian immunodeficiency virus (SIV). We discovered that the viral strain used for infection determines the replicative capacity in microglial cells as well as the extent of neuropathological lesions and the occurrence of neurological symptoms. Moreover, the viral load in the brain parenchyma correlated with the development of overt neurological disease whereas the one in plasma did not. By comparing the viral load in three different compartments, we demonstrated that the viral burden in the CSF is influenced both by the viral replication in the periphery as well as in the brain parenchyma. According to these results, it is not the absolute amount of viral load in the CSF but rather the viral antigen contributed by the viral production within the brain which correlates with the development of neurological disease. In longitudinal studies, we observed that this autochthonous virus production, as evidenced by a ratio of the viral load in CSF to the one in plasma, takes place for a prolonged period of time before overt neurological signs are manifested. This finding suggests that this ratio could be used as a prognostic marker for immunodeficiency virus-induced neurological disease.     

Biologie

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Allgemeines

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