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  • 1
    Language: English
    In: Molecular microbiology, 2007, Vol.66(1), pp.26-39
    Description: Virulence of nontypeable Haemophilus influenzae (NTHi) is dependent on the decoration of lipooligosaccharide with sialic acid. This sugar must be derived from the host, as NTHi cannot synthesize sialic acids. NTHi can also use sialic acid as a carbon source. The genes encoding the sialic acid transporter and the genes encoding the catabolic activities are localized to two divergently transcribed operons, the siaPT operon and the nan operon respectively. In this study, we identified SiaR as a repressor of sialic acid transport and catabolism in NTHi. Inactivation of siaR resulted in the unregulated expression of the genes in both operons. Unregulated catabolism of sialic acid in the siaR mutant resulted in the reduction of surface sialylation and an increase in serum sensitivity. In addition to SiaR-mediated repression, CRP, the cAMP receptor protein, was shown to activate expression of the siaPT operon but not the nan operon. We describe a model in which SiaR and CRP work to modulate intracellular sialic acid levels. Our results demonstrate the importance of SiaR-mediated regulation to balance the requirement of surface sialylation and the toxic accumulation of intracellular sialic acid. ; Includes references ; p. 26-39.
    Keywords: Cyclic Adenosine Monophosphate;
    ISSN: 0950-382X
    E-ISSN: 13652958
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  • 2
    In: Molecular Microbiology, July 1996, Vol.21(1), pp.13-19
    Description: The haemolysin of Haemophilus ducreyi is the newest member of the Proteus/Serratia family of pore‐forming toxins. In order to assess the role of the haemolysin in virulence, we constructed an isogenic haemolysin‐deficient mutant of H. ducreyi strain 35000. This strain, designated 35000‐3, lacks detectable haemolytic activity. We tested H. ducreyi strains 35000 and 35000‐3 for their cytopathic activity against human foreskin fibroblasts (HFFs). We observed strong cytopathic activity when strain 35000 was co‐cultured with HFFs. In contrast, cytopathic activity was not observed when strain 35000‐3 was co‐cultured with HFF cells. We also analysed the isogenic pair of H. ducreyi strains for cytopathic activity against HeLa cells and the keratinocyte cell line HaCaT. Strains 35000 and 35000‐3 were strongly cytotoxic when co‐cultured with HeLa cells. HaCaT monolayers were slightly damaged by cocultivation with strain 35000‐3 but this damage was much less than that observed when HaCaT cells were cocultured with strain 35000. These results indicate that the H. ducreyi haemolysin is responsible for the previously observed cytotoxic activity against HFF cells and is partially responsible for the activity observed with HaCaT cells. The haemolysin, however, is not responsible for the activity observed with HeLa cells.
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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