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David M Gordon

Publications and source records attributed to David M Gordon.

17 recordsLinked to original sources
PubMed2026

PheBee: A Graph-Aware System for Scalable, Traceable, and Semantic Phenotyping.

OBJECTIVES: Phenotype-driven workflows in clinical and translational research require standardized ontology-based representation, ontology-aware cohort discovery, and provenance inspection for each assertion. Existing approaches optimize either for semantic traversal or scalable batch analytics, but not both. We describe PheBee, a hybrid system that links semantic assertions to scalable evidence storage via a deterministic identifier, preserving provenance while supporting ontology-aware discovery at cohort scale. MATERIALS AND METHODS: PheBee represents phenotype assertions in a knowledge graph as ontology-linked nodes with clinical modifier context (e.g., negated, family history), and stores supporting evidence records in a scalable row-oriented evidence table for cohort-scale access. The two layers are connected by a deterministic identifier enabling stable joins across repeated ingestions without duplicating high-volume evidence in the graph. We evaluated PheBee using synthetic datasets designed to exercise end-to-end ingestion and query workflows. RESULTS: Functional evaluation validated hierarchical term expansion, qualifier-aware retrieval, duplicate-free assertion handling under re-ingestion, and privacy-conscious management of subjects shared across multiple research projects. At scale (10,000 subjects producing 12M evidence records) PheBee completed ingestion in ~30 minutes and responded to interactive queries within 6 seconds under concurrent load. DISCUSSION: PheBee exposes a unified API for ontology-aware cohort discovery with hierarchical term expansion, subject-centric retrieval of phenotypes and clinical modifiers, and evidence and provenance queries. Its data model aligns with GA4GH Phenopackets, facilitating interoperability with phenotype exchange standards. CONCLUSION: By combining ontology-aware semantics with scalable, provenance-bearing evidence storage, PheBee provides a practical open-source foundation for phenotype-driven research workflows that demand both semantic precision and cohort-scale traceability.

cohort studies↗
PubMed2006

A naturally occurring novel allele of Escherichia coli outer membrane protein A reduces sensitivity to bacteriophage.

A novel Escherichia coli outer membrane protein A (OmpA) was discovered through a proteomic investigation of cell surface proteins. DNA polymorphisms were localized to regions encoding the protein's surface-exposed loops which are known phage receptor sites. Bacteriophage sensitivity testing indicated an association between bacteriophage resistance and isolates having the novel ompA allele.

Alleles↗
PubMed2006

Bacteriocin diversity and the frequency of multiple bacteriocin production in Escherichia coli.

A collection of 266 faecal isolates of Escherichia coli from humans was assayed for the production of mitomycin C-inducible bacteriocins and screened using a PCR-based method for the presence of eleven colicins and seven microcins. Eight different colicins were detected and all seven microcins. Of the strains examined, 38 % produced a bacteriocin, 24 % produced a colicin and 20 % produced a microcin. Of the 102 bacteriocin-producing strains, 42 % produced one type of bacteriocin, 41 % produced two, 16 % produced three and one strain was found to produce four different bacteriocins. Strains producing more than one bacteriocin were more likely to be members of E. coli genetic group B2 and less likely to belong to genetic groups A or D. Several of the bacteriocins were found to co-occur in a strain more often than would be expected by chance: microcins H47 and M; colicin Ia and microcin V; colicins B and M; colicins E1 and M; colicins E1 and Ia. No bacteriocins released as a consequence of cell lysis were found to co-associate more often than expected by chance. Three non-mutually exclusive hypotheses are presented that might explain the high frequency of multiple bacteriocin production in E. coli strains: (1) expanded killing range, (2) expanded receptor repertoire and (3) fitness benefits in different environments.

Biodiversity↗
PubMed2005

Influence of the age and sex of human hosts on the distribution of Escherichia coli ECOR groups and virulence traits.

Escherichia coli were isolated from the faeces of 266 individuals living in the Canberra region of Australia. The isolates were characterized for their ECOR group membership (A, B1, B2 or D) and for the presence of 29 virulence-associated traits. Overall, 19.5 % of the strains were members of group A, 12.4 % B1, 45.1 % B2 and 22.9 % D. The frequency with which strains belonging to the four ECOR groups were observed varied with the age and sex of the hosts from which they were isolated. In males, the probability of isolating A or D strains increased with host age, whilst the probability of detecting a group B2 strain declined. In females, the probability of recovering A or B2 strains increased with increasing host age and there was a concomitant decline in the likelihood of isolating B1 or D strains. Of the 29 virulence-associated traits examined, 24 were detected in more than one strain. The likelihood of detecting most traits varied with a strain's ECOR membership, with the exception of afa/draBC, astA, cvaC, eaeA, iss and iutA, for which there was no statistically significant evidence of an association with ECOR group. The frequency with which fimH, iha, eaeA, iroN, hlyD, iss, ompT and K1 were detected in a strain depended on the age or sex of the host from which the strain was isolated. In group B2 strains many of the virulence traits were non-randomly associated, with some co-occurring in a strain less often than expected by chance, whilst others were co-associated. In 17 cases, the extent to which two virulence traits were co-associated was found to depend on host sex and age. The results of this study suggest that the morphological, physiological and dietary differences that occur among human individuals of different sex or age may influence the distribution of E. coli genotypes.

Adolescent↗
PubMed2005

Phenotypic and genotypic characterization of encapsulated Escherichia coli isolated from blooms in two Australian lakes.

Escherichia coli has long been used as an indicator organism for water quality assessment. Recently there has been an accumulation of evidence that suggests some strains of this organism are able to proliferate in the environment, a characteristic that would detract from its utility as an indicator of faecal pollution. Phenotypic and genotypic characterization of E. coli isolated from blooms in two Australian lakes, separated by a distance of approximately 200 km, identified that the blooms were dominated by three E. coli strains. A major phenotypic similarity among the three bloom strains was the presence of a group 1 capsule. Genetic characterization of a conserved region of the cps gene cluster, which encodes group 1 capsules, identified a high degree of genetic variation within the bloom isolates. This differs from previously described encapsulated E. coli strains which are highly conserved at the cps locus. The phenotypic or genotypic profiles of the bloom strains were not identified in 435 E. coli strains isolated from vertebrates. The occurrence of these encapsulated strains suggests that some E. coli have evolved a free-living lifestyle and do not require a host in order to proliferate. The presence of the same three strains in bloom events in different geographical regions of a temperate climate, and at different times, indicates that free-living E. coli strains are able to persist in these water reservoirs. This study provides further evidence of circumstances where caution is required in using E. coli as an indicator organism for water quality.

Australian Capital Territory↗
PubMed2004

Diversity analysis of commensal porcine Escherichia coli - associations between genotypes and habitat in the porcine gastrointestinal tract.

Diversity studies of enteric Escherichia coli have relied almost entirely on faecal isolations on the assumption that they are representative of flora found throughout the gastrointestinal tract. The authors have addressed this belief by analysing isolates obtained from the duodenum, ileum, colon and faeces of pigs. E. coli isolates were obtained from eight pigs and characterized using multi-locus enzyme electrophoresis and PCR-based screening for a range of factors thought to be associated with intestinal and extra-intestinal disease. There are four main genetic groups of commensal E. coli (A, B1, B2, D). Group A strains represented 76 % of the isolates from the duodenum, ileum and colon compared to 58 % of the strains isolated from faeces. A nested molecular analysis of variance based on the allozyme and virulence factor screening results showed that differences among individual pigs accounted for 6 % of the observed genetic diversity, whilst 27 % of the genetic variation could be explained by clonal composition differences among gut regions. Finally, the absence of virulence genes in these commensals indicates that they may be suitable as a probiotic consortium, particularly if they also display increased adherence to enterocytes and antagonistic activity against pathogenic strains of E. coli.

Animals↗
PubMed2004

Evolution of multi-resistance plasmids in Australian clinical isolates of Escherichia coli.

Plasmids allow the movement of genetic material, including antimicrobial resistance genes, between bacterial species and genera. They frequently mediate resistance to multiple antimicrobials and can result in the acquisition by a pathogen of resistance to all or most clinically relevant antimicrobials. Unfortunately, there are still large gaps in our understanding of how new multi-resistance plasmids evolve. Five Australian clinical institutions collaborated in this study of multi-resistance plasmids in clinical isolates of Escherichia coli. We characterized 72 resistance plasmids in terms of the antimicrobial resistance profile they conferred, their size and their incompatibility group. Restriction fragment length polymorphisms were used to determine the genetic relationships between the plasmids. Relationships between the host cells were determined using multi-locus enzyme electrophoresis. A lack of correlation between the evolutionary history of the host cells and their plasmids suggests that the horizontal transfer of resistance plasmids between strains of E. coli is common. The resistance plasmids were very diverse, with a wide range of resistance profiles and a lack of discrete evolutionary lineages. Multi-resistance plasmids did not evolve via the co-integrative capture of smaller resistance plasmids; rather, the roles of recombination and the horizontal movement of mobile genetic elements appeared to be most important.

Anti-Bacterial Agents↗
PubMed2004

Coliform dynamics and the implications for source tracking.

In many parts of the world, coliform counts in recreational waters are unacceptably high. In an attempt to rectify this problem, programmes are under way to develop methods that will allow the sources of the faecal contamination thought to be responsible for these elevated counts to be identified. The success of these efforts depends on the validity of several assumptions that underlie many of the proposed methods. One of the critical assumptions is that the clonal composition of the coliform species being monitored in a water body reflects the clonal composition of the species in the host populations responsible for the faecal inputs into that water body. To determine the extent to which among-strain variation in a coliform species might invalidate this assumption, a series of simple mathematical models was proposed and analysed. The first series of models assumed that all cells of species were identical. The question posed was - is the density of a coliform species in a body of water linearly related to the rate at which cells of the species enter the water body via faecal production? The results of these models suggest that, over a wide range of conditions, cell densities in the water body are linearly related to the rate at which cells enter the water body as a result of faecal contamination. This outcome occurs whether or not cells are capable of division in the external environment. When the rate of cell division depends on the concentration of available nutrients then, when nutrient input rates are 'high' and rates of faecal contamination are 'low', this linear relationship does not hold. The second series of models assumed that the coliform species consists of different strains and that these strains differ in their performance in the external environment. The results of these multistrain models show that the relative abundance of strains in the external environment is unlikely to reflect their relative abundance in the faecal inputs to the environment. Consequently, statements such as - domestic animals are responsible for 30% and wildlife for 70% of the faecal inputs to a water body - may well be meaningless.

Animals↗
PubMed2003

Species differences in plasmid carriage in the Enterobacteriaceae.

Modern concerns about the spread of antibiotic resistance raise questions about the effect of bacterial species on plasmid evolution and maintenance. We studied 223 Enterobacteriaceae isolated from wild mammals and determined the number of plasmids per isolate, the size of those plasmids, and the distribution of plasmid incompatibility groups N, P, W, FII, and A/C. All of these variables were non-randomly distributed with respect to bacterial species, suggesting that host-cell factors constrain the plasmids that a strain will carry. The implication for the evolution of multiple-resistance plasmids in a clinical setting is that although inter-generic plasmid transfer may introduce a novel resistance plasmid into a bacterial genus, it is likely to be modified to suit the requirements of the new host cell. This then further suggests that resistance plasmids will evolve independent lineages within bacterial species although the genes incorporated in them may have come from the same original source.

Animals↗
PubMed2003

Genetic and ecological structure of Hafnia alvei in Australia.

Multilocus enzyme electrophoresis of 161 Hafnia alvei isolates from 158 hosts and 3 water column samples collected in Australia revealed that this species consists of two genetically distinct groups. The two groups of H. alvei differed significantly in their genetic structure and host distribution. The taxonomic class of the host but not geographic locality explained a significant proportion of the observed genetic and biochemical variation among strains within each genetic group.

Australia↗
PubMed2003

The distribution and genetic structure of Escherichia coli in Australian vertebrates: host and geographic effects.

Escherichia coli was isolated from more than 2300 non-domesticated vertebrate hosts living in Australia. E. coli was most prevalent in mammals, less prevalent in birds and uncommon in fish, frogs and reptiles. Mammals were unlikely to harbour E. coli if they lived in regions with a desert climate and less likely to have E. coli if they lived in the tropics than if they lived in semi-arid or temperate regions. In mammals, the likelihood of isolating E. coli from an individual depended on the diet of the host and E. coli was less prevalent in carnivores than in herbivores or omnivores. In both birds and mammals, the probability of isolating E. coli increased with the body mass of the host. Hosts living in close proximity to human habitation were more likely to harbour E. coli than hosts living away from people. The relative abundance of E. coli groups A, B1, B2 and D strains in mammals depended on climate, host diet and body mass. Group A strains were uncommon, but were isolated from both ectothermic and endothermic vertebrates. Group B1 strains could also be isolated from any vertebrate group, but were predominant in ectothermic vertebrates, birds and carnivorous mammals. Group B2 strains were unlikely to be isolated from ectotherms and were most abundant in omnivorous and herbivorous mammals. Group D strains were rare in ectotherms and uncommon in endotherms, but were equally abundant in birds and mammals. The results of this study suggest that, at the species level, the ecological niche of E. coli is mammals with hindgut modifications to enable microbial fermentation, or in the absence of a modified hindgut, E. coli can only establish a population in 'large-bodied' hosts. The non-random distribution of E. coli genotypes among the different host groups indicates that strains of the four E. coli groups may differ in their ecological niches and life-history characteristics.

Animals↗
PubMed2002

The influence of host dynamics on the clonal composition of Escherichia coli populations.

Species, be they plant or animal, vary in their capacity for population growth or decline. Populations of the same species may also differ in their capacity for population change. A series of mathematical models were developed with the aim of determining if host population dynamics could influence the clonal composition of the Escherichia coli community in that host population. The biological assumptions underlying the models are described in some detail. Analytical and numerical approaches were used to investigate the behaviour of these models. The results demonstrate that host dynamics can have a profound influence on the E. coli clonal composition of the host population. This outcome is largely independent of the nature of the assumptions underlying the models. The ways in which the predictions of these models may be tested empirically are discussed, as are the implications of these models for understanding the nature of host-bacterial pathogen dynamics.

Animals↗
PubMed2002

The genetic structure of Escherichia coli populations in primary and secondary habitats.

Escherichia coli were recovered from the members of two two-person households and their associated septic tanks. The E. coli were isolated using selective and non-selective isolation techniques, characterized using the method of multi-locus enzyme electrophoresis and screened for the presence of virulence factors associated with extra-intestinal disease by using PCR. The growth rate-temperature relationships of strains from the two habitats were also determined. Temporal variation explained 25% of the observed electrophoretic type (ET) diversity in the humans. Among-host variation accounted for 29% of the observed allelic diversity. In one household, ET diversity of the E. coli population in the septic tank was significantly lower than ET diversity in the humans providing the inputs to the septic tank. Molecular analysis of variance revealed that, on average, strains recovered from the septic tank of this household were genetically distinct from strains recovered from the humans providing the faecal inputs to the septic tank. Further, the growth rate-temperature response of strains differed between strains isolated from the septic tank and strains isolated from the humans. Septic tank isolates grew better at low temperatures than strains isolated from humans, but more slowly at high temperatures compared to the human isolates. By contrast, no real differences in ET diversity, allelic diversity, or the growth characteristics of strains could be detected between strains from the humans and strains from the septic tank of the other household. The results of this study suggest there are strains of E. coli that are better "adapted" to conditions found in the external environment compared to strains isolated from the gastrointestinal habitat. Further, the finding that the numerically dominant clones and clonal diversity in secondary habitats can differ substantially from those found in the source populations will confound efforts to identify the sources of faecal pollution in the environment.

Environment↗
PubMed1999

A theoretical and empirical investigation of the invasion dynamics of colicinogeny.

A mathematical model describing the dynamics of a colicinogenic and a colicin-sensitive population propagated under serial transfer culture conditions was formulated. In addition, a series of in vitro invasion experiments using six representatives of the E colicin group was undertaken, together with the estimation of the growth rates and colicinogenic characteristics of the strains. Growth rates among the strains varied by up to 44%. There were 14-fold differences among strains in their lysis rates and there were up to 10-fold differences in the amount of colicin produced per lysed cell. The in vitro serial transfer invasion experiments revealed that regardless of initial frequency all colicinogenic strains succeeded in displacing the sensitive cell populations. The amount of time required for the colicin-sensitive cell population to be displaced declined as the initial frequency of the colicinogenic population increased and strains producing higher titres of colicin tended to displace the sensitive strain more rapidly. Overall, the observed dynamics of the invasion of colicinogenic strains was adequately described by the theoretical model. However, despite there being substantial differences among the strains in their growth rates and colicinogenic characteristics there were relatively few differences, observed or predicted, in the invasion dynamics of the six colicinogenic strains. These results suggest that the characteristics of different colicinogenic strains cannot be used to explain the extensive variation in the relative abundance of different colicins in natural populations of bacteria.

Bacteriolysis↗
PubMed1998

Temporal changes in the frequency of colicinogeny in Escherichia coli from house mice.

Escherichia coli was isolated from feral house mice (Mus domesticus) during the course of a mouse plague in the state of Victoria, Australia. The isolates were characterized for the production of colicins and their resistance to the co-occurring colicins. Of the 447 isolates examined, 59% were found to be colicinogenic. Phenotypic and PCR-based genotypic methods were used to determine the types of colicins being produced. Colicin E2 was the most common, representing 27% of the colicin-producing isolates. Colicin Ia was produced by 3% of the colicinogenic isolates. The remaining colicins could not be identified, but phenotypic and PCR data argue that at least nine different colicin types are present in this collection of E. coli. The frequency of colicinogenic isolates declined from 71% to 43% over the 7 months of the study. All colicin types appeared to decline in frequency. Concurrently, the resistance of isolates to colicin E2 increased from about 50% to 70%. Two hypotheses are proposed to explain the decline in the frequency of colicinogeny in this population of E. coli. The first relates to the within-host interactions occurring among colicinogenic, colicin-susceptible and colicin-resistant populations within a host. The second relates to the among-host interactions between susceptible and colicinogenic populations and the effect of host population densities on these interactions.

Animals↗
PubMed1997

The genetic structure of Escherichia coli populations in feral house mice.

Escherichia coli was isolated from feral house mice (Mus domesticus) during the course of a mouse plague in the state of Victoria, Australia. Two farms were sampled over a period of 7 months and a total of 447 isolates were collected. The isolates were characterized using the techniques of randomly amplified polymorphic DNA and multi-locus enzyme electrophoresis. The mean genetic diversity of this E. coli population (H = 0.24) was found to be substantially lower than the diversity of an E. col population reported elsewhere for a single human host. Analysis of the allozyme data revealed that there were significant differences in the relative abundance of genotypes between the two localities sampled and among sample dates. Overall, however, spatial and temporal effects accounted for less than 5% of the genotypic diversity. Allele frequencies and the relative abundance of the more common genotypes did not differ between male and female hosts. The number of genotypes and genotype diversity increased as the age of the host increased, suggesting that the mice are continuing to acquire new E. coli clones throughout their life. The frequency of some alleles changed with respect to host age, which indicates that clone acquisition may not be a random process. It is argued that the low level of genetic diversity observed in this population of E. coli reflects the boom and bust nature of mouse population density in this region of Australia.

Alleles↗