Biomedical subjects

Paul A Hoskisson

Publications and source records attributed to Paul A Hoskisson.

8 recordsLinked to original sources

PubMed2006

MtrAB-LpqB: a conserved three-component system in actinobacteria?

Streptomyces coelicolor is the model organism for the actinobacteria, a group of high-GC Gram-positive bacteria with members that are notable both for their industrial importance as antibiotic producers and for their pathogenicity. The S. coelicolor genome encodes a subgroup of sensor kinases that is genetically linked to lipoprotein genes, at least one of which functions as an accessory protein to its co-translated kinase. Another member of this subgroup, MtrB, is widely conserved in the actinobacteria, along with its presumed cognate response regulator MtrA and the lipoprotein LpqB. Here, we postulate a possible role for LpqB in the MtrAB signal transduction pathway. We discuss what is known about this pathway in the actinobacteria and offer insights into why an essential response regulator does not necessarily need its cognate sensor kinase for activation.

ATP-Binding Cassette Transporters↗

PubMed2006

Expression of Cre recombinase during transient phage infection permits efficient marker removal in Streptomyces.

We report a system for the efficient removal of a marker flanked by two loxP sites in Streptomyces coelicolor, using a derivative of the temperate phage phiC31 that expresses Cre recombinase during a transient infection. As the test case for this recombinant phage (called Cre-phage), we present the construction of an in-frame deletion of a gene, pglW, required for phage growth limitation or Pgl in S.coelicolor. Cre-phage was also used for marker deletion in other strains of S.coelicolor.

Bacteriophages↗

PubMed2006

Geological history and within-island diversity: a debris avalanche and the Tenerife lizard Gallotia galloti.

Several processes have been described that could explain geographical variation and speciation within small islands, including fragmentation of populations through volcanic eruptions. Massive landslides, or debris avalanches, could cause similar effects. Here we analyse the potential impact of the 0.8 million-year-ago (Ma) Güimar valley debris avalanche on the phylogeography of the lizard Gallotia galloti on the Canary Island of Tenerife. Distributions of mitochondrial DNA lineages (based on cytochrome b sequences) were analysed on a 60-km southeastern coast transect centred on this area. Three main clades were detected, which can be divided into northern (one clade) and southern (two clades) groups that introgress across the valley. Maximum-likelihood estimates of migration rates (scaled for mutation rate) revealed highly asymmetric patterns, indicating that long-term gene flow into this region from both the northern and the southern populations greatly exceeded that in the opposite directions, consistent with recolonization of the area. The ancestral Tenerife node on the G. galloti tree is estimated at 0.80 Ma, matching closely with the geological estimate for the debris avalanche. Morphological variation (body dimensions and scalation) was also analysed and indicated a stepped cline in female scalation across the valley, although the patterns for male scalation and male and female body dimensions were not as clear. Together these findings provide support for the hypothesis that the debris avalanche has shaped the phylogeography of G. galloti and may even have been a primary cause of the within-island cladogenesis through population fragmentation and isolation. Current estimates of timing of island unification mean that the original hypothesis that within-island diversity is explained by the secondary contact of populations from the two ancient precursor islands of Teno and Anaga is less plausible for this and some other Tenerife species. Large-scale landslides have occurred on many volcanic islands, and so may have been instrumental in shaping within-island diversities.

Animal Migration↗

PubMed2006

DevA, a GntR-like transcriptional regulator required for development in Streptomyces coelicolor.

The gram-positive filamentous bacterium Streptomyces coelicolor has a complex developmental cycle with three distinct phases: growth of the substrate mycelium, development of reproductive structures called aerial hyphae, and differentiation of these aerial filaments into long chains of exospores. During a transposon mutagenesis screen, we identified a novel gene (devA) required for proper development. The devA mutant produced only rare aerial hyphae, and those that were produced developed aberrant spore chains that were much shorter than wild-type chains and had misplaced septa. devA encodes a member of the GntR superfamily, a class of transcriptional regulators that typically respond to metabolite effector molecules. devA forms an operon with the downstream gene devB, which encodes a putative hydrolase that is also required for aerial mycelium formation on R5 medium. S1 nuclease protection analysis showed that transcription from the single devA promoter was temporally associated with vegetative growth, and enhanced green fluorescent protein transcriptional fusions showed that transcription was spatially confined to the substrate hyphae in the wild type. In contrast, devAB transcript levels were dramatically upregulated in a devA mutant and the devA promoter was also active in aerial hyphae and spores in this background, suggesting that DevA might negatively regulate its own production. This suggestion was confirmed by gel mobility shift assays that showed that DevA binds its own promoter region in vitro.

Amino Acid Sequence↗

PubMed2005

Differentiation and protease production in Micromonospora echinospora (ATCC 15837).

Micromonospora echinospora differentiates in both submerged and surface cultures producing abundant dark spores after a period of vegetative mycelial growth. In submerged batch cultures, under either carbon or nitrogen limiting conditions, protease activity was found to coincide with sporulation indicating a relationship between proteolytic activity and differentiation in this organism. Further evidence for this link was provided from surface grown cultures wherein sporulation was inhibited by the serine protease inhibitors TLCK and TPCK. The association between proteolysis and differentiation apparent in this organism correlates with evidence of a similar phenomenon observed in the streptomycetes, suggesting that this may be a common response associated with differentiation in filamentous actinomycetes.

Kinetics↗

PubMed2005

Continuous culture--making a comeback?

The heyday of continuous culture was in the 1960s, when its versatility and reproducibility were used to address fundamental problems in diverse microbiological fields such as biochemistry, ecology, genetics and physiology. The advent of molecular genetics in the 1970s and 1980s led to a decline in the popularity of continuous culture as a standard laboratory tool. The current trend of studying global proteomics, transcriptomics and metabolomics requires reproducible, reliable and biologically homogeneous datasets with which to approach a given problem. The use of continuous culture techniques can aid the acquisition of such data, and continuous cultures offer advantages over biologically heterogeneous batch cultures, where secondary growth and stress effects can often mask subtle physiological differences and trends. This review is intended to remind microbiologists of the value of continuous cultivation in a wide range of biological investigations, and describes some advantages and recent advances in applications of continuous culture in post-genomic studies.

Bacteria↗

PubMed2004

Modulation of glycogen and trehalose levels in Micromonospora echinospora (ATCC 15837).

The growth of Micromonospora echinospora was studied in high and low C/N ratio medium using both batch and continuous culture. Asparagine was consumed rapidly in batch cultures where it served as both a nitrogen and carbon source. Glucose consumption was low suggesting that asparagine functions as the major carbon source under these conditions. The effect of nutrient limitation on the accumulation of storage carbohydrate in batch culture revealed an intimate association between nitrogen limitation and the accumulation of carbonaceous reserves. This study revealed that glycogen constituted the major carbohydrate reserve associated with the onset of sporulation. Intracellular trehalose levels were found to be relatively low and may have been affected by the availability of carbon. Continuous culture studies revealed a correlation between glycogen accumulation and increasing growth rate. It was also found that elevated cellular ATP levels correlated with the increase in glycogen, and reduced glycolytic activity. At the higher growth rates cellular ATP levels were elevated and coincided with reduced activity of the key glycolytic enzyme, phosphofructokinase, suggesting that glycogen can act as a convenient energy reservoir when excess carbon flux dictates.

Adenosine Triphosphate↗

PubMed2004

Sensing and responding to diverse extracellular signals? Analysis of the sensor kinases and response regulators of Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a Gram-positive soil bacterium that undergoes a complex developmental life cycle. The genome sequence of this organism was recently completed and has revealed the presence of over 60 sigma factors and a multitude of other transcriptional regulators, with a significant number of these being putative two-component signal transduction proteins. The authors have used the criteria established by Hoch and co-workers (Fabret et al., 1999, J Bacteriol 181, 1975-1983) to identify sensor kinase and response regulator genes encoded within the S. coelicolor genome. This analysis has revealed the presence of 84 sensor kinase genes, 67 of which lie adjacent to genes encoding response regulators. This strongly suggests that these paired genes encode two-component systems. In addition there are 13 orphan response regulators encoded in the genome, several of which have already been characterized and are implicated in development and antibiotic production, and 17 unpaired and as yet uncharacterized sensor kinases. This article attempts to infer useful information from sequence analysis and reviews what is currently known about the two-component systems, unpaired sensor kinases and orphan response regulators of S. coelicolor from both published reports and the authors' own unpublished data.

Adaptation, Physiological↗