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The effects of local spatial structure on epidemiological invasions.

Predicting the likely success of invasions is vitally important in ecology and especially epidemiology. Whether an organism can successfully invade and persist in the short-term is highly dependent on the spatial correlations that develop in the early stages of invasion. By modelling the correlations between individuals, we are able to understand the role of spatial heterogeneity in invasion dynamics without the need for large-scale computer simulations. Here, a natural methodology is developed for modelling the behaviour of individuals in a fixed network. This formulation is applied to the spread of a disease through a structured network to determine invasion thresholds and some statistical properties of a single epidemic.

Communicable Disease Control↗

The arcABC operon required for fermentative growth of Pseudomonas aeruginosa on arginine: Tn5-751-assisted cloning and localization of structural genes.

Pseudomonas aeruginosa is able to utilize L-arginine as the energy source for growth under anaerobic, nitrate-free conditions. Mutations in the chromosomal arcABC gene cluster specifying the inducible arginine deiminase pathway enzymes abolish fermentative growth on arginine. From two different arc::Tn5-751 insertion mutants of P. aeruginosa recombinant plasmids have been derived which carry a resistance marker of transposon Tn5-751 plus flanking parts of the arc region. These recombinant plasmids served to reconstruct in vitro the functional arcABC cluster on a 5.6 kb fragment, which was inserted into the broad-host-range vector pKT240. In P. aeruginosa this 5.6 kb segment complemented arcABC mutations in trans and contained the control region necessary in cis for arc enzyme induction by oxygen limitation and arginine. The results of subcloning experiments and transcriptional lacZ fusions, the polarity of transposon insertions and the effect of external promoters led to the conclusion that the structural genes arcA (for arginine deiminase), arcB (for catabolic ornithine carbamoyltransferase) and arcC (for carbamate kinase) are contiguous and transcribed in the same direction. Thus, the arcABC cluster appears to have the characteristics of an operon. In Escherichia coli the cloned arcABC genes were expressed at low, non-inducible levels; strong vector promoters enhanced arc expression up to 100-fold. This indicates that transcriptional initiation at the arc promoter(s) is poor in E. coli.

Arginine↗

Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p.

Lack of the yeast Rrm3p DNA helicase causes replication defects at multiple sites within ribosomal DNA (rDNA), including at the replication fork barrier (RFB). These defects were unaltered in rrm3 sir2 cells. When the RFB binding Fob1p was deleted, rrm3-generated defects at the RFB were eliminated, but defects at other rDNA sites were not affected. Thus, specific protein-DNA complexes make replication Rrm3p-dependent. Because rrm3-induced increases in recombination and cell cycle length were only partially suppressed in rrm3 fob1 cells, which still required checkpoint and fork restart activities for viability, non-RFB rrm3-induced defects contribute to rDNA fragility and genome instability.

Binding Sites↗