Three genetic groups of the Eucalyptus stem canker pathogen Teratosphaeria zuluensis introduced into Africa from an unknown source.

The Eucalyptus stem canker pathogen Teratosphaeria zuluensis was discovered in South Africa in 1988 and it has subsequently been found in several other African countries as well as globally. In this study, the population structure, genetic diversity and evolutionary history of T. z uluensis were analysed using microsatellite markers to gain an enhanced understanding of its movement in Africa. Isolates were collected from several sites in Malawi, Mozambique, Uganda and Zambia. Data obtained were compared with those previously published for a South African population. The data obtained from 334 isolates, amplified across eight microsatellite loci, were used for assignment, differentiation and genetic diversity tests. STRUCTURE analyses, θ st and genetic distances revealed the existence of two clusters, one dominated by isolates from South Africa and the other by isolates from the Zambezi basin including Malawi, Mozambique and Zambia. High levels of admixture were found within and among populations, dominated by the Mulanje population in Malawi. Moderate to low genetic diversity of the populations supports the previously held view that the pathogen was introduced into Africa. The clonal nature of the Ugandan population suggests a very recent introduction, most likely from southern Africa.

Modelling the immunopathogenesis of HIV-1 infection and the effect of multidrug therapy: the role of fusion inhibitors in HAART.

There is currently tremendous effort being directed at developing potent, highly active antiretroviral therapies that can effectively control HIV- 1 infection without the need for continuous, lifelong use of these drugs. In the ongoing search for powerful antiretroviral agents that can affect sustained control for HIV infection, mathematical models can help in assessing both the correlates of protective immunity and the clinical role of a given drug regimen as well as in understanding the efficacy of drug therapies administered at different stages of the disease. In this study, we develop a new mathematical model of the immuno-pathogenesis of HIV-1 infection, which we use to assess virological responses to both intracellular and extracellular antiretroviral drugs. We first develop a basic mathematical model of the immuno-pathogenesis of HIV-1 infection that incorporates three distinct stages in the infection cycle of HIV-1: entry of HIV-1 into the cytoplasm of CD4+ T cells, transcription of HIV-1 RNA to DNA within CD4+ T cells, and production of HIV-1 viral particles within CD4+ T cells. Then we extend the basic model to incorporate the effect of three major categories of anti-HIV-1 drugs: fusion/entry inhibitors (FIs), reverse transcriptase inhibitors (RTIs), and protease inhibitors (PIs). Model analysis establishes that the actual drug efficacy of FIs, gamma and of PIs, kappa is the same as their effective efficacies while the effective drug efficacy for the RTIs, gamma (upsilon ) , is dependent on the rate of transcription of the HIV-1 RNA to DNA, and the lifespan of infected CD4+ T cells where virions have only entered the cytoplasm and that this effective efficacy is less than the actual efficacy, upsilon. Our studies suggest that, of the three anti-HIV drug categories (FIs, RTIs, and PIs), any drug combination of two drugs that includes RTIs is the weakest in the control of HIV-1 infection.

Esterases and putative lipases from tropical isolates of Aureobasidium pullulans.

Esterases and lipases have been studied in a number of fungi, though very little is known about esterases from Aureobasidium pullulans especially from the African tropics. In this study, forty-two Zimbabwean isolates were screened for lipase activity on tributyrin agar. Extracellular esterase activities of seven selected isolates were studied under varying conditions using para-nitrophenol acetate as substrate. Twenty isolates (48%) showed lipolytic activity; sixteen showed negative results for lipase activity while the rest showed weak activities. Esterase activities in broth cultures ranged from 0.011-0.223 mmol/microg protein/min while activities ranged from 1.5-12.8 U/ml under solid state fermentation. The esterases were optimally active at pH 7.6-8.0, showed a temperature optimum of 35 degrees C and retained more than 50% activity at temperatures up to 60 degrees C and at pH 4.0-7.0 after 150 min. Enzyme production was optimal after 5-6 days with diammonium hydrogen phosphate as nitrogen source. Isolates showed variations in preference for carbon source for esterase production. The A. pullulans esterases differed from most fungal esterases in that they are optimally active in alkaline conditions and are active over a broad pH range.

Modelling the human immune response mechanisms to mycobacterium tuberculosis infection in the lungs.

This work elaborates on the effects of cytotoxic lymphocytes (CTLs) and other immune mechanisms in determining whether a TB-infected individual will develop active or latent TB. It answers one intriguing question: why do individuals infected with Mycobacterium tuberculosis (Mtb) experience different clinical outcomes? In addressing this question, we have developed a model that captures the effects of CTLs and the combined effects of CD4+ helper T cells (Th1 and Th2) immune response mechanisms to TB infection. The occurrence of active or latent infection is shown to depend on a number of factors that include effector function and levels of CTLs. We use the model to predict disease progression scenarios, including primary, latency or clearance. Model analysis shows that occurrence of active disease is much attributed to the Mtb pathogen ability to persist outside the intracellular environment and that high levels of CTLs result in latent TB, while low levels of CTLs result in active TB. This is attributed to the CTLs' ability to directly kill infected macrophages and the bacteria inside the infected macrophages. The study suggests directions for further basic studies and potential new treatment strategies.

Molecular characterisation of Armillaria species from Zimbabwe.

Armillaria species are amongst the most important pathogens of trees and have a world-wide distribution. In recent years, the taxonomy of Northern Hemisphere Armillaria spp. has been extensively treated, but those occurring in Africa are poorly known. Previously, isolates of Armillaria from Zimbabwe have been grouped based on morphology and biochemical tests. In this study, six isolates representing the three previously characterized groups of Armillaria spp. occurring in Zimbabwe were analysed using DNA-based techniques. Three distinct clusters emerged from both PCR-RFLP and analysis of sequence data for the IGS-1 rRNA operon. The three groups corresponded to those previously identified based on morphology and biochemical tests. Differences in IGS-1 sequences strongly suggest that the Zimbabwean groups represent three distinct taxa. Isolates belonging to Group I, previously assumed to be to A. heimii, were similar to those identified as A. fuscipes from South Africa and La Reunion. Group II isolates resided in a clade apart from all other isolates and appear to represent A. heimii. The remaining isolates residing in Group III clustered with isolates from Zambia and Cameroon. These are different from A. heimii and A. fuscipes and apparently represent an undescribed taxon.