14 research outputs found
Metabolic Networks of Sodalis glossinidius: A Systems Biology Approach to Reductive Evolution
Background: Genome reduction is a common evolutionary process affecting bacterial lineages that establish symbiotic or pathogenic associations with eukaryotic hosts. Such associations yield highly reduced genomes with greatly streamlined metabolic abilities shaped by the type of ecological association with the host. Sodalis glossinidius, the secondary endosymbiont of tsetse flies, represents one of the few complete genomes available of a bacterium at the initial stages of this process. In the present study, genome reduction is studied from a systems biology perspective through the reconstruction and functional analysis of genome-scale metabolic networks of S. glossinidius. Results: The functional profile of ancestral and extant metabolic networks sheds light on the evolutionary events underlying transition to a host-dependent lifestyle. Meanwhile, reductive evolution simulations on the extant metabolic network can predict possible future evolution of S. glossinidius in the context of genome reduction. Finally, knockout simulations in different metabolic systems reveal a gradual decrease in network robustness to different mutational events for bacterial endosymbionts at different stages of the symbiotic association. Conclusions: Stoichiometric analysis reveals few gene inactivation events whose effects on the functionality of S. glossinidius metabolic systems are drastic enough to account for the ecological transition from a free-living to hostdependent lifestyle. The decrease in network robustness across different metabolic systems may be associated with th
Primary pulmonary hypertension, Raynaud’s phenomenon and generalised vasculitis in juvenile rheumatoid arthritis
Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine
Cyclic AMP inhibits and putrescine represses expression of the speA gene encoding biosynthetic arginine decarboxylase in Escherichia coli
Monofluorophosphate Is a Selective Inhibitor of Respiratory Sulfate-Reducing Microorganisms
Despite
the environmental and economic cost of microbial sulfidogenesis
in industrial operations, few compounds are known as selective inhibitors
of respiratory sulfate reducing microorganisms (SRM), and no study
has systematically and quantitatively evaluated the selectivity and
potency of SRM inhibitors. Using general, high-throughput assays to
quantitatively evaluate inhibitor potency and selectivity in a model
sulfate-reducing microbial ecosystem as well as inhibitor specificity
for the sulfate reduction pathway in a model SRM, we screened a panel
of inorganic oxyanions. We identified several SRM selective inhibitors
including selenate, selenite, tellurate, tellurite, nitrate, nitrite,
perchlorate, chlorate, monofluorophosphate, vanadate, molydate, and
tungstate. Monofluorophosphate (MFP) was not known previously as a
selective SRM inhibitor, but has promising characteristics including
low toxicity to eukaryotic organisms, high stability at circumneutral
pH, utility as an abiotic corrosion inhibitor, and low cost. MFP remains
a potent inhibitor of SRM growing by fermentation, and MFP is tolerated
by nitrate and perchlorate reducing microorganisms. For SRM inhibition,
MFP is synergistic with nitrite and chlorite, and could enhance the
efficacy of nitrate or perchlorate treatments. Finally, MFP inhibition
is multifaceted. Both inhibition of the central sulfate reduction
pathway and release of cytoplasmic fluoride ion are implicated in
the mechanism of MFP toxicity