HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650–1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.

Bacterial resistance to antibiotics usually incurs a fitness cost in the absence of selecting drugs, and this cost of resistance plays a key role in the spread of antibiotic resistance in pathogen populations. Costs of resistance have been shown to vary with environmental conditions, but the causes of this variability remain obscure. In this article, we show that the average cost of rifampicin resistance in the pathogenic bacterium Pseudomonas aeruginosa is reduced by the addition of ribosome inhibitors (chloramphenicol or streptomycin) that indirectly constrain transcription rate and therefore reduce demand for RNA polymerase activity. This effect is consistent with predictions from metabolic control theory. We also tested the alternative hypothesis that the observed trend was due to a general effect of environmental quality on the cost of resistance. To do this we measured the fitness of resistant mutants in the presence of other antibiotics (ciprofloxacin and carbenicillin) that have similar effects on bacterial growth rate but bind to different target enzymes (DNA gyrase and penicillin-binding proteins, respectively) and in 41 singlecarbon source environments of varying quality. We find no consistent effect of environmental quality on the average cost of resistance in these treatments. These results show that the cost of rifampicin resistance varies with demand for the mutated target enzyme, rather than as a simple function of bacterial growth rate or stress.

Bioinformatic screening and PCR-based approaches detected active infection with human hepegivirus-1 in exposed populations.

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The importance of recombination in the evolution and genetic diversity of the hepatitis C virus (HCV) is currently uncertain. Only a small number of intergenotypic recombinants have been identified so far, and each has core and envelope genes classified as belonging to genotype 2. Here, we investigated two putative genotype 4/1 recombinants from southern Cameroon using a number of approaches, including standard Sanger sequencing, genotype-specific PCR amplification, and non-HCV-specific Illumina RNA sequencing (RNA-seq). Recombination between genotypes 1 and 4 was confirmed in both samples, and the parental lineages of each recombinant belong to HCV subtypes that are cocirculating at a high prevalence in Cameroon. Using the RNA-seq approach, we obtained a complete genome for one sample, which contained a recombination breakpoint at the E2/P7 gene junction. We developed and applied a new method, called Deep SimPlot, which can be used to visualize and identify viral recombination directly from the short sequence reads created by next-generation sequencing in conjunction with a consensus sequence.