Biomedical subjects

Bruce A McDonald

Publications and source records attributed to Bruce A McDonald.

9 recordsLinked to original sources

PubMed2006

Significant difference in pathogenicity between MAT1-1 and MAT1-2 isolates in the wheat pathogen Mycosphaerella graminicola.

Five Mycosphaerella graminicola populations from four geographic regions (Australia, Israel, Switzerland, and the USA) were assayed for neutral RFLP markers and mating type idiomorphs. On average, 25-30 genetically distinct isolates were selected from each population and their pathogenicity was measured on two wheat cultivars in a common garden experiment conducted in a greenhouse. A significant difference in pathogenicity was found between MAT1-1 and MAT1-2 isolates. On average, MAT1-1 isolates had 14-22% greater pathogenicity than MAT1-2 isolates. The pattern of higher pathogenicity in MAT1-1 isolates was consistent across four geographical populations and on two wheat cultivars. A uniform and continuous variation in pathogenicity was found among isolates within each mating type, but no genetic differentiation in selectively neutral RFLP loci was found between mating types, consistent with the hypothesis that differences in pathogenicity were not due to the effects of specific pathogenicity genes or non-random genetic backgrounds.

Ascomycota↗

PubMed2006

Origin and domestication of the fungal wheat pathogen Mycosphaerella graminicola via sympatric speciation.

The Fertile Crescent represents the center of origin and earliest known place of domestication for many cereal crops. During the transition from wild grasses to domesticated cereals, many host-specialized pathogen species are thought to have emerged. A sister population of the wheat-adapted pathogen Mycosphaerella graminicola was identified on wild grasses collected in northwest Iran. Isolates of this wild grass pathogen from 5 locations in Iran were compared with 123 M. graminicola isolates from the Middle East, Europe, and North America. DNA sequencing revealed a close phylogenetic relationship between the pathogen populations. To reconstruct the evolutionary history of M. graminicola, we sequenced 6 nuclear loci encompassing 464 polymorphic sites. Coalescence analyses indicated a relatively recent origin of M. graminicola, coinciding with the known domestication of wheat in the Fertile Crescent around 8,000-9,000 BC. The sympatric divergence of populations was accompanied by strong genetic differentiation. At the present time, no genetic exchange occurs between pathogen populations on wheat and wild grasses although we found evidence that gene flow may have occurred since genetic differentiation of the populations.

Ascomycota↗

PubMed2006

Emergence of a new disease as a result of interspecific virulence gene transfer.

New diseases of humans, animals and plants emerge regularly. Enhanced virulence on a new host can be facilitated by the acquisition of novel virulence factors. Interspecific gene transfer is known to be a source of such virulence factors in bacterial pathogens (often manifested as pathogenicity islands in the recipient organism) and it has been speculated that interspecific transfer of virulence factors may occur in fungal pathogens. Until now, no direct support has been available for this hypothesis. Here we present evidence that a gene encoding a critical virulence factor was transferred from one species of fungal pathogen to another. This gene transfer probably occurred just before 1941, creating a pathogen population with significantly enhanced virulence and leading to the emergence of a new damaging disease of wheat.

Animals↗

PubMed2006

Global migration patterns in the fungal wheat pathogen Phaeosphaeria nodorum.

The global migration patterns of the fungal wheat pathogen Phaeosphaeria nodorum were analysed using 12 microsatellite loci. Analysis of 693 isolates from nine populations indicated that the population structure of P. nodorum is characterized by high levels of genetic diversity and a low degree of subdivision between continents. To determine whether genetic similarity of populations was a result of recent divergence or extensive gene flow, the microsatellite data were analysed using an isolation-with-migration model. We found that the continental P. nodorum populations diverged recently, but that enough migration occurred to reduce population differentiation. The migration patterns of the pathogen indicate that immigrants originated mainly from populations in Europe, China and North America.

Alleles↗

PubMed2004

Evidence for subdivision of the root-endophyte Phialocephala fortinii into cryptic species and recombination within species.

The genetic structure of the root-endophyte Phialocephala fortinii was analyzed in three study sites using 11 single-copy RFLP probes. A total of 541 strains isolated from surface-sterilized, fine roots (diameter 0.5-3 mm) of Norway spruce (Picea abies) were examined. The average gene diversity (H) was high in all three study sites. Cluster analysis showed that up to four well-separated clusters of multi-locus haplotypes were present within the sites. Significant population subdivision was detected among these clusters, suggesting that groups of multi-locus haplotypes were reproductively isolated and that P. fortinii is a species complex composed of several cryptic species. This hypothesis was supported by ISSR-PCR which showed clusters consistent with those of the multi-locus haplotypes identified by RFLP analysis. In contrast, ITS sequence analysis did not allow to separate the species as clearly. The index of association (IA) did not deviate significantly from zero within any cryptic species, suggesting that recombination occurs within these species. Cryptic species occurred sympatrically. Thalli of two cryptic species were detected in the same 5-mm-long root segment in one instance. No significant differentiation was observed among populations of the same cryptic species in forest stands located approximately 5 km from each other. This finding is consistent with significant gene flow over this spatial scale. In addition, several isolates with both identical multi-locus haplotype and identical ISSR fingerprint were found at each study site indicating genotype flow or a recent common history between study sites.

Ascomycota↗

PubMed2004

Molecular population genetic analysis differentiates two virulence mechanisms of the fungal avirulence gene NIP1.

Deletion or alteration of an avirulence gene are two mechanisms that allow pathogens to escape recognition mediated by the corresponding resistance gene in the host. We studied these two mechanisms for the NIP1 avirulence gene in field populations of the fungal barley pathogen Rhynchosporium secalis. The product of the avirulence gene, NIP1, causes leaf necrosis and elicits a defense response on plants with the Rrs1 resistance gene. A high NIP1 deletion frequency (45%) was found among 614 isolates from different geographic populations on four continents. NIP1 was also sequenced for 196 isolates, to identify DNA polymorphisms and corresponding NIP1 types. Positive diversifying selection was found to act on NIP1. A total of 14 NIP1 types were found, 11 of which had not been described previously. The virulence of the NIP1 types was tested on Rrs1 and rrs1 barley lines. Isolates carrying three of these types were virulent on the Rrs1 cultivar. One type each was found in California, Western Europe, and Jordan. Additionally, a field experiment with one pair of near-isogenic lines was conducted to study the selection pressure imposed by Rrs1 on field populations of R. secalis. Deletion of NIP1 was the only mechanism used to infect the Rrs1 cultivar in the field experiment. In this first comprehensive study on the population genetics of a fungal avirulence gene, virulence to Rrs1 in R. secalis was commonly achieved through deletion of the NIP1 avirulence gene but rarely also through point mutations in NIP1.

Amino Acid Sequence↗

PubMed2003

Further evidence for sexual reproduction in Rhynchosporium secalis based on distribution and frequency of mating-type alleles.

Rhynchosporium secalis, the causal agent of scald on barley, is thought to be exclusively asexual because no teleomorph has been found. Partial sequences of the HMG-box and alpha-domain of Rhynchosporium secalis isolates were identified and used to develop a PCR assay for the mating-type locus. PCR amplification of only one of these two domains was possible in each strain, suggesting that R. secalis has a MAT organization that is similar to other known heterothallic fungi. A multiplex PCR with primers amplifying either a MAT1-1- or MAT1-2-specific amplicon was used to determine the distribution of mating types in several R. secalis populations. In total, 1101 isolates from Australia, Switzerland, Ethiopia, Scandinavia, California, and South Africa were included in the analysis. Mating types occurred in equal frequencies for most of these populations, suggesting frequency-dependent selection consistent with sexual reproduction. In addition, both mating types were frequently found occupying the same lesion or leaf, providing opportunities for isolates of opposite mating type to interact and reproduce sexually. We propose that R. secalis should be considered a sexual pathogen, although the sexual cycle may occur infrequently in some populations.

Ascomycota↗

PubMed2003

Physiologic data acquisition system and database for the study of disease dynamics in the intensive care unit.

OBJECTIVE: To describe a real-time, continuous physiologic data acquisition system for the study of disease dynamics in the intensive care unit. DESIGN: Descriptive report. SETTING: A 16-bed pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: A total of 170 critically ill or injured pediatric patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: We describe a computerized data acquisition and analysis system for the study of critical illness and injury from the perspective of complex dynamic systems. Both parametric (1 Hz) and waveform (125-500 Hz) signals are recorded and analyzed. Waveform data include electrocardiogram, respiration, systemic arterial pressure (invasive and noninvasive), central venous pressure, pulmonary arterial pressure, left and right atrial pressures, intracranial pressure, body temperature, and oxygen saturation. Details of the system components are explained and examples are given from the resultant physiologic database of signal processing algorithms and signal analyses using linear and nonlinear metrics. CONCLUSIONS: We have successfully developed a real-time, continuous physiologic data acquisition system that can capture, store, and archive data from pediatric intensive care unit patients for subsequent time series analysis of dynamic changes in physiologic state. The physiologic signal database generated from this system is available for analysis of dynamic changes caused by critical illness and injury.

Algorithms↗

PubMed2002

Pathogen population genetics, evolutionary potential, and durable resistance.

We hypothesize that the evolutionary potential of a pathogen population is reflected in its population genetic structure. Pathogen populations with a high evolutionary potential are more likely to overcome genetic resistance than pathogen populations with a low evolutionary potential. We propose a flexible framework to predict the evolutionary potential of pathogen populations based on analysis of their genetic structure. According to this framework, pathogens that pose the greatest risk of breaking down resistance genes have a mixed reproduction system, a high potential for genotype flow, large effective population sizes, and high mutation rates. The lowest risk pathogens are those with strict asexual reproduction, low potential for gene flow, small effective population sizes, and low mutation rates. We present examples of high-risk and low-risk pathogens. We propose general guidelines for a rational approach to breed durable resistance according to the evolutionary potential of the pathogen.

Bacteria↗