Now showing items 21-40 of 8304

    • A practical microwave method for the synthesis of fluoromethy 4-methylbenzenesulfonate in tert-amyl alcohol

      Brocklesby, K.L.; Waby, Jennifer S.; Cawthorne, C.; Smith, G. (2018-04-25)
      Fluorine substitution is an established tool in medicinal chemistry to favourably alter the molecular properties of a lead compound of interest. However, gaps still exist in the library of synthetic methods for accessing certain fluorine-substituted motifs. One such area is the fluoromethyl group, particularly when required in a fluoroalkylating capacity. The cold fluorination of methylene ditosylate is under evaluated in the literature, often proceeding with low yields or harsh conditions. This report describes a novel microwave method for the rapid nucleophilic fluorination of methylene ditosylate using inexpensive reagents in good isolated yield (65%).
    • Does the bilingual advantage extend to trilingualism?

      Guðmundsdóttir, Margaret D.; Lesk, Valerie E. (Taylor and Francis, 2019)
      This study examined whether the proposed bilingual advantage in inhibitory control and working memory can be extended to a trilingual advantage, and assessed any age-related effects on a continuum in young adults to older adults. Trilinguals, bilinguals and monolinguals’ performance on the Simon task and a numerical version of the N-back task was compared. On the Simon task, there was no language group difference observed, although the data show an age-related decline in inhibitory control only in trilinguals, but not in bilinguals or monolinguals. No clear language group differences were observed between trilinguals and bilinguals on the N-back task, however an overall trilingual and bilingual disadvantage, compared to monolinguals, was observed. Together the results suggest that managing two or three languages, compared to just one, may have a negative impact on inhibitory control and working memory performance. Importantly, they highlight the need to control for a possible confounding effect of including trilinguals/multilinguals in bilingual cohorts and to ensure that participants in monolingual cohorts speak only one language.
    • Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations.

      Lempens, P.; Meehan, Conor J.; Vandelannoote, K.; Fissette, K.; de Rijk, P.; Van Deun, A.; Rigouts, L.; de Jong, B.C. (2018-02-19)
      The majority of Mycobacterium tuberculosis isolates resistant to isoniazid harbour a mutation in katG. Since these mutations cause a wide range of minimum inhibitory concentrations (MICs), largely below the serum level reached with higher dosing (15 mg/L upon 15–20 mg/kg), the drug might still remain partly active in presence of a katG mutation. We therefore investigated which genetic mutations predict the level of phenotypic isoniazid resistance in clinical M. tuberculosis isolates. To this end, the association between known and unknown isoniazid resistance-conferring mutations in whole genome sequences, and the isoniazid MICs of 176 isolates was examined. We found mostly moderate-level resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr mutation, and always very high MICs (≥19.2 mg/L) for the combination of katG Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c-15t alone, partly also showed moderate-level resistance, particularly when combined with inhA Ser94Ala. No overt association between low-confidence or unknown mutations, except in katG, and isoniazid resistance (level) was found. Except for the rare katG deletion, line probe assay is thus not sufficiently accurate to predict the level of isoniazid resistance for a single mutation in katG or inhA.
    • Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues

      Meehan, Conor J.; Goig, G.A.; Kohl, T.A.; Verboven, L.; Dippenaar, A.; Ezewudo, M.; Farhat, M.R.; Guthrie, J.L.; Laukens, K.; Miotto, P.; et al. (2019-09)
      Whole genome sequencing (WGS) of Mycobacterium tuberculosis has rapidly progressed from a research tool to a clinical application for the diagnosis and management of tuberculosis and in public health surveillance. This development has been facilitated by drastic drops in cost, advances in technology and concerted efforts to translate sequencing data into actionable information. There is, however, a risk that, in the absence of a consensus and international standards, the widespread use of WGS technology may result in data and processes that lack harmonization, comparability and validation. In this Review, we outline the current landscape of WGS pipelines and applications, and set out best practices for M. tuberculosis WGS, including standards for bioinformatics pipelines, curated repositories of resistance-causing variants, phylogenetic analyses, quality control and standardized reporting.
    • Storage of Sputum in Cetylpyridinium Chloride, OMNIgene.SPUTUM, and Ethanol Is Compatible with Molecular Tuberculosis Diagnostic Testing

      Sanoussi, C.N.; de Jong, B.C.; Affolabi, D.; Meehan, Conor J.; Odoun, M.; Rigouts, L. (2019-07)
      We compared cetylpyridinium chloride (CPC), ethanol (ETOH), and OMNIgene.SPUTUM (OMNI) for 28-day storage of sputum at ambient temperature before molecular tuberculosis diagnostics. Three sputum samples were collected from each of 133 smear-positive tuberculosis (TB) patients (399 sputum samples). Each patient's sputum was stored with either CPC, ETOH, or OMNI for 28 days at ambient temperature, with subsequent rpoB amplification targeting a short fragment (81 bp, GeneXpert MTB/RIF [Xpert]) or a long fragment (1,764 bp, in-house nested PCR). For 36 patients, Xpert was also performed at baseline on all 108 fresh sputum samples. After the 28-day storage (D28), Xpert positivity did not significantly differ between storage methods. In contrast, higher positivity for rpoB nested PCR was obtained with OMNI (n = 125, 94%) than with ETOH (n = 114, 85.7%; P = 0.001). Smears with scanty acid-fast bacilli (AFB) had lower rpoB PCR positivity with ETOH storage (n = 10, 41.7%) than with CPC (n = 16, 66.7%; difference, 25%; 95% confidence interval [CI], 3.5 to 46.5; P = 0.031) or OMNI (n = 16, 69.6%; difference, 26.1%; 95% CI, 3.8 to 48.4; P = 0.031), with no difference between CPC and OMNI. Poststorage, the threshold cycle (CT ) values significantly decreased compared to those prestorage with ETOH (difference, -1.1; 95% CI, -1.6 to -0.6; P = 0.0001) but not with CPC (P = 0.915) or OMNI (P = 0.33). For one patient's ETOH- and CPC-stored specimens with a CT of <10, Xpert gave results of rifampin false resistant at D28, which was resolved by repeating Xpert on a 1/100 diluted specimen. In conclusion, 28-day storage of sputum in OMNI, CPC, or ETOH at ambient temperature does not impact short-fragment PCR (Xpert), including for low smear grades. However, for long-fragment PCR, ETOH yielded a lower PCR positivity for low smear grades, while the performance of OMNI and CPC was excellent for all smear grades. (The study has been registered at under registration number NCT02744469.).
    • GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions

      Farhat, M.R.; Freschi, L.; Calderon, R.; Ioerger, T.; Snyder, M.; Meehan, Conor J.; de Jong, B.; Rigouts, L.; Sloutsky, A.; Kaur, D.; et al. (2019-05-13)
      Drug resistance diagnostics that rely on the detection of resistance-related mutations could expedite patient care and TB eradication. We perform minimum inhibitory concentration testing for 12 anti-TB drugs together with Illumina whole-genome sequencing on 1452 clinical Mycobacterium tuberculosis (MTB) isolates. We evaluate genome-wide associations between mutations in MTB genes or non-coding regions and resistance, followed by validation in an independent data set of 792 patient isolates. We confirm associations at 13 non-canonical loci, with two involving non-coding regions. Promoter mutations are measured to have smaller average effects on resistance than gene body mutations. We estimate the heritability of the resistance phenotype to 11 anti-TB drugs and identify a lower than expected contribution from known resistance genes. This study highlights the complexity of the genomic mechanisms associated with the MTB resistance phenotype, including the relatively large number of potentially causal loci, and emphasizes the contribution of the non-coding portion of the genome.
    • Superimposing incident sexually transmitted infections on HIV phylogram to investigate possible misclassification of men who have sex with men as heterosexuals in a cohort in Antwerp, Belgium

      Osbak, K.K.; Meehan, Conor J.; G. Ribas, S.; Heyndrickx, L.; Ariën, K.K.; Tsoumanis, A.; Florence, E.; Esbroeck, M.V.; Fransen, K.; Kenyon, C.R. (2019-04)
      In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only remained significant for heterosexuals with syphilis (P = 0.001). Under closer scrutiny, this association was driven by six heterosexual men who were located in six almost exclusively MSM clusters. A parsimonious conclusion is that these six individuals were potentially misclassified as heterosexual. Improving the accuracy of sexual behaviour reporting could improve care.
    • Female sterility associated with increased clonal propagation suggests a unique combination of androdioecy and asexual reproduction in populations of Cardamine amara (Brassicaceae)

      Tedder, Andrew; Helling, M.; Pannell, J.R.; Shimizu-Inatsugi, R.; Kawagoe, T.; van Campen, J.; Sese, J.; Shimizu, K.K. (2015-04)
      The coexistence of hermaphrodites and female-sterile individuals, or androdioecy, has been documented in only a handful of plants and animals. This study reports its existence in the plant species Cardamine amara (Brassicaceae), in which female-sterile individuals have shorter pistils than seed-producing hermaphrodites. Morphological analysis, in situ manual pollination, microsatellite genotyping and differential gene expression analysis using Arabidopsis microarrays were used to delimit variation between female-sterile individuals and hermaphrodites. Female sterility in C. amara appears to be caused by disrupted ovule development. It was associated with a 2.4- to 2.9-fold increase in clonal propagation. This made the pollen number of female-sterile genets more than double that of hermaphrodite genets, which fulfils a condition of co-existence predicted by simple androdioecy theories. When female-sterile individuals were observed in wild androdioecious populations, their ramet frequencies ranged from 5 to 54 %; however, their genet frequencies ranged from 11 to 29 %, which is consistent with the theoretically predicted upper limit of 50 %. The results suggest that a combination of sexual reproduction and increased asexual proliferation by female-sterile individuals probably explains the invasion and maintenance of female sterility in otherwise hermaphroditic populations. To our knowledge, this is the first report of the coexistence of female sterility and hermaphrodites in the Brassicaceae.
    • Evolution of the Selfing Syndrome in Arabis alpina (Brassicaceae)

      Tedder, Andrew; Carleial, S.; Gołębiewska, M.; Kappel, C.; Shimizu, K.K.; Stift, M. (2015-06-03)
      Introduction The transition from cross-fertilisation (outcrossing) to self-fertilisation (selfing) frequently coincides with changes towards a floral morphology that optimises self-pollination, the selfing syndrome. Population genetic studies have reported the existence of both outcrossing and selfing populations in Arabis alpina (Brassicaceae), which is an emerging model species for studying the molecular basis of perenniality and local adaptation. It is unknown whether its selfing populations have evolved a selfing syndrome. Methods Using macro-photography, microscopy and automated cell counting, we compared floral syndromes (size, herkogamy, pollen and ovule numbers) between three outcrossing populations from the Apuan Alps and three selfing populations from the Western and Central Alps (Maritime Alps and Dolomites). In addition, we genotyped the plants for 12 microsatellite loci to confirm previous measures of diversity and inbreeding coefficients based on allozymes, and performed Bayesian clustering. Results and Discussion Plants from the three selfing populations had markedly smaller flowers, less herkogamy and lower pollen production than plants from the three outcrossing populations, whereas pistil length and ovule number have remained constant. Compared to allozymes, microsatellite variation was higher, but revealed similar patterns of low diversity and high Fis in selfing populations. Bayesian clustering revealed two clusters. The first cluster contained the three outcrossing populations from the Apuan Alps, the second contained the three selfing populations from the Maritime Alps and Dolomites. Conclusion We conclude that in comparison to three outcrossing populations, three populations with high selfing rates are characterised by a flower morphology that is closer to the selfing syndrome. The presence of outcrossing and selfing floral syndromes within a single species will facilitate unravelling the genetic basis of the selfing syndrome, and addressing which selective forces drive its evolution.
    • Local adaptation (mostly) remains local: reassessing environmental associations of climate-related candidate SNPs in Arabidopsis halleri

      Rellstab, C.; Fischer, M.C.; Zoller, S.; Tedder, Andrew; Shimizu, K.K.; Widmer, A.; Holderegger, R.; Gugerli, F. (2017-02)
      Numerous landscape genomic studies have identified single-nucleotide polymorphisms (SNPs) and genes potentially involved in local adaptation. Rarely, it has been explicitly evaluated whether these environmental associations also hold true beyond the populations studied. We tested whether putatively adaptive SNPs in Arabidopsis halleri (Brassicaceae), characterized in a previous study investigating local adaptation to a highly heterogeneous environment, show the same environmental associations in an independent, geographically enlarged set of 18 populations. We analysed new SNP data of 444 plants with the same methodology (partial Mantel tests, PMTs) as in the original study and additionally with a latent factor mixed model (LFMM) approach. Of the 74 candidate SNPs, 41% (PMTs) and 51% (LFMM) were associated with environmental factors in the independent data set. However, only 5% (PMTs) and 15% (LFMM) of the associations showed the same environment-allele relationships as in the original study. In total, we found 11 genes (31%) containing the same association in the original and independent data set. These can be considered prime candidate genes for environmental adaptation at a broader geographical scale. Our results suggest that selection pressures in highly heterogeneous alpine environments vary locally and signatures of selection are likely to be population-specific. Thus, genotype-by-environment interactions underlying adaptation are more heterogeneous and complex than is often assumed, which might represent a problem when testing for adaptation at specific loci.
    • Tapping the Vast Potential of the Data Deluge in Small-scale Food-Animal Production Businesses: Challenges to Near Real-time Data Analysis and Interpretation

      Vial, F.; Tedder, Andrew (2017-09-06)
      Food-animal production businesses are part of a data-driven ecosystem shaped by stringent requirements for traceability along the value chain and the expanding capabilities of connected products. Within this sector, the generation of animal health intelligence, in particular, in terms of antimicrobial usage, is hindered by the lack of a centralized framework for data storage and usage. In this Perspective, we delimit the 11 processes required for evidence-based decisions and explore processes 3 (digital data acquisition) to 10 (communication to decision-makers) in more depth. We argue that small agribusinesses disproportionally face challenges related to economies of scale given the high price of equipment and services. There are two main areas of concern regarding the collection and usage of digital farm data. First, recording platforms must be developed with the needs and constraints of small businesses in mind and move away from local data storage, which hinders data accessibility and interoperability. Second, such data are unstructured and exhibit properties that can prove challenging to its near real-time preprocessing and analysis in a sector that is largely lagging behind others in terms of computing infrastructure and buying into digital technologies. To complete the digital transformation of this sector, investment in rural digital infrastructure is required alongside the development of new business models to empower small businesses to commit to near real-time data capture. This approach will deliver critical information to fill gaps in our understanding of emerging diseases and antimicrobial resistance in production animals, eventually leading to effective evidence-based policies.
    • Genetic basis and timing of a major mating system shift in Capsella.

      Bachmann, J.A.; Tedder, Andrew; Laenen, B.; Fracassetti, M.; Désamoré, A.; Lafon-Placette, C.; Steige, K.A.; Callot, C.; Marande, W.; Neuffer, B.; et al. (2019-06)
      A crucial step in the transition from outcrossing to self-fertilization is the loss of genetic self-incompatibility (SI). In the Brassicaceae, SI involves the interaction of female and male speci-ficity components, encoded by the genesSRKandSCRat the self-incompatibility locus (S-lo-cus). Theory predicts thatS-linked mutations, and especially dominant mutations inSCR, arelikely to contribute to loss of SI. However, few studies have investigated the contribution ofdominant mutations to loss of SI in wild plant species. Here, we investigate the genetic basis of loss of SI in the self-fertilizing crucifer speciesCapsella orientalis, by combining genetic mapping, long-read sequencing of completeS-hap-lotypes, gene expression analyses and controlled crosses. We show that loss of SI inC. orientalisoccurred<2.6 Mya and maps as a dominant trait totheS-locus. We identify a fixed frameshift deletion in the male specificity geneSCRand con-firm loss of male SI specificity. We further identify anS-linked small RNA that is predicted tocause dominance of self-compatibility. Our results agree with predictions on the contribution of dominantS-linked mutations toloss of SI, and thus provide new insights into the molecular basis of mating system transitions.
    • Demography and mating system shape the genome-wide impact of purifying selection in Arabis alpina

      Laenen, B.; Tedder, Andrew; Nowak, M.D.; Toräng, P.; Wunder, J.; Wötsel, S.; Steige, K.A.; Kourmpetis, Y.; Odong, T.; Drouzas, A.D.; et al. (2018-01-23)
      Plant mating systems have profound effects on levels and structuring of genetic variation and can affect the impact of natural selection. Although theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study the effect of mating system on purifying selection by conducting population-genomic analyses on whole-genome resequencing data from 38 European individuals of the arctic-alpine crucifer Arabis alpina. We find that outcrossing and mixed-mating populations maintain genetic diversity at similar levels, whereas highly self-fertilizing Scandinavian A. alpina show a strong reduction in genetic diversity, most likely as a result of a postglacial colonization bottleneck. We further find evidence for accumulation of genetic load in highly self-fertilizing populations, whereas the genome-wide impact of purifying selection does not differ greatly between mixed-mating and outcrossing populations. Our results demonstrate that intermediate levels of outcrossing may allow efficient selection against harmful alleles, whereas demographic effects can be important for relaxed purifying selection in highly selfing populations. Thus, mating system and demography shape the impact of purifying selection on genomic variation in A. alpina. These results are important for an improved understanding of the evolutionary consequences of mating system variation and the maintenance of mixed-mating strategies.
    • Targeted long-read sequencing of a locus under long-term balancing selection in Capsella

      Bachmann, J.A.; Tedder, Andrew; Laenen, B.; Steige, K.A.; Slotte, T. (2018-04)
      Rapid advances in short-read DNA sequencing technologies have revolutionized population genomic studies, but there are genomic regions where this technology reaches its limits. Limitations mostly arise due to the difficulties in assembly or alignment to genomic regions of high sequence divergence and high repeat content, which are typical characteristics for loci under strong long-term balancing selection. Studying genetic diversity at such loci therefore remains challenging. Here, we investigate the feasibility and error rates associated with targeted long-read sequencing of a locus under balancing selection. For this purpose, we generated bacterial artificial chromosomes (BACs) containing the Brassicaceae S-locus, a region under strong negative frequency-dependent selection which has previously proven difficult to assemble in its entirety using short reads. We sequence S-locus BACs with single-molecule long-read sequencing technology and conduct de novo assembly of these S-locus haplotypes. By comparing repeated assemblies resulting from independent long-read sequencing runs on the same BAC clone we do not detect any structural errors, suggesting that reliable assemblies are generated, but we estimate an indel error rate of 5.7×10−5. A similar error rate was estimated based on comparison of Illumina short-read sequences and BAC assemblies. Our results show that, until de novo assembly of multiple individuals using long-read sequencing becomes feasible, targeted long-read sequencing of loci under balancing selection is a viable option with low error rates for single nucleotide polymorphisms or structural variation. We further find that short-read sequencing is a valuable complement, allowing correction of the relatively high rate of indel errors that result from this approach.
    • Identifying Archaeological Bone via Non-Destructive ZooMS and the Materiality of Symbolic Expression: Examples from Iroquoian Bone Points

      McGrath, K.; Rowsell, K.; Gates St-Pierre, C.; Tedder, Andrew; Foody, G.; Roberts, C.; Speller, C.; Collins, M. (2019-07-30)
      Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology.
    • The Inherent Tensions within Sustainable Supply Chains: A Case Study from Bangladesh

      Shareef, M.A.; Dwivedi, Y.K.; Kumar, V.; Mahmud, R.; Hughes, D.L.; Kizgin, Hatice (Francis and Taylor, 2019)
      The complexities surrounding the supply chain logistics for perishable commodities within Bangladesh are extensive. Poor infrastructure, fragmented transportation and corruption compound the operational complexities within this emerging market. This case study analyses many of the day-to-day operational challenges and tensions inherent within Micro-Small-Medium Enterprises (MSMEs) forming the backbone of the Bangladesh socio-economic structure. The drive for transition toward greater levels of sustainability and corporate responsibility is problematic, affecting many levels within an extended and fragmented supply chain. The selected case study highlights the “lived in” geographical, environmental, economic and cultural factors that impact the ability of emerging market enterprises to remain profitable within emergency scenarios whilst transitioning toward a more sustainable model. This study, whilst detailing many of the tensions and critical issues facing MSMEs, highlights the benefits of direct Government intervention, criticality of a leaner and more efficient supply chain and reassessment of financial incentives to drive the transition to a more efficient and sustainable economy.
    • Comparative Genomics Shows That Mycobacterium ulcerans Migration and Expansion Preceded the Rise of Buruli Ulcer in Southeastern Australia.

      Buultjens, A.H.; Vandelannoote, K.; Meehan, Conor J.; Eddyani, M.; de Jong, B.C.; Fyfe, J.A.M.; Globan, M.; Tobias, N.J.; Porter, J.L.; Tomita, T.; et al. (2018-04-01)
      Since 2000, cases of the neglected tropical disease Buruli ulcer, caused by infection with Mycobacterium ulcerans, have increased 100-fold around Melbourne (population 4.4 million), the capital of Victoria, in temperate southeastern Australia. The reasons for this increase are unclear. Here, we used whole-genome sequence comparisons of 178 M. ulcerans isolates obtained primarily from human clinical specimens, spanning 70 years, to model the population dynamics of this pathogen from this region. Using phylogeographic and advanced Bayesian phylogenetic approaches, we found that there has been a migration of the pathogen from the east end of the state, beginning in the 1980s, 300 km west to the major human population center around Melbourne. This move was then followed by a significant increase in M. ulcerans population size. These analyses inform our thinking around Buruli ulcer transmission and control, indicating that M. ulcerans is introduced to a new environment and then expands, rather than it being from the awakening of a quiescent pathogen reservoir.
    • The Repetitive Element RLEP Is a Highly Specific Target for Detection of Mycobacterium leprae

      Braet, S.; Vandelannoote, K.; Meehan, Conor J.; Brum Fontes, A.N.; Hasker, E.; Rosa, P.S.; Lucena-Silva, R.N.; Rigouts, L.; Suffys, P.N.; de Jong, B.C. (2018)
    • Interactions in the microbiome: communities of organisms and communities of genes

      Boon, E.; Meehan, Conor J.; Whidden, C.; Wong, D. H.-J.; Langille, M.G.I.; Beiko, R.G. (2014-01-01)
      A central challenge in microbial community ecology is the delineation of appropriate units of biodiversity, which can be taxonomic, phylogenetic, or functional in nature. The term ‘community’ is applied ambiguously; in some cases, the term refers simply to a set of observed entities, while in other cases, it requires that these entities interact with one another. Microorganisms can rapidly gain and lose genes, potentially decoupling community roles from taxonomic and phylogenetic groupings. Trait-based approaches offer a useful alternative, but many traits can be defined based on gene functions, metabolic modules, and genomic properties, and the optimal set of traits to choose is often not obvious. An analysis that considers taxon assignment and traits in concert may be ideal, with the strengths of each approach offsetting the weaknesses of the other. Individual genes also merit consideration as entities in an ecological analysis, with characteristics such as diversity, turnover, and interactions modeled using genes rather than organisms as entities. We identify some promising avenues of research that are likely to yield a deeper understanding of microbial communities that shift from observation-based questions of ‘Who is there?’ and ‘What are they doing?’ to the mechanistically driven question of ‘How will they respond?’
    • Mycobacterium ulcerans Population Genomics to Inform on the Spread of Buruli Ulcer across Central Africa

      Vandelannoote, K.; Phanzy, D.M.; Kibadi, K.; Eddyani, M.; Meehan, Conor J.; Jordaens, K.; Leirs, H.; Portaels, F.; Stinear, T.P.; Harris, S.R.; et al. (2019-02)
      Buruli ulcer is a neglected tropical disease of skin and subcutaneous tissue caused by infection with the pathogen Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical village scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all Buruli ulcer foci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineage of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the Buruli ulcer epidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium.