Biology subjects

Borrell, S.

Publications and source records attributed to Borrell, S..

22 records · Page 2Linked to original sources

bioRxiv2018

Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.\n\nWe utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).\n\nOne MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.\n\nThe genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

evolutionary biology↗

bioRxiv2018

Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity

Large sequence datasets are difficult to visualize and handle. Additionally, they are often not an adequate representation of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases. Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity.\n\nTreemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity.

bioinformatics↗

bioRxiv2017

Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa

BackgroundUnderstanding transmission dynamics is useful for tuberculosis (TB) control. We conducted a population-based molecular epidemiological study to understand TB transmission in Ghana.\n\nMethodsMycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively-sampled pulmonary TB patients between July, 2012 and December, 2015 were confirmed as MTBC using IS6110 PCR. MTBC lineages were identified by large sequence polymorphism and single nucleotide polymorphism assays and further characterized using spoligotyping and standard 15-loci MIRU-VNTR typing. We used the n-1 method to estimate recent TB transmission and identified associated risk factors using logistic regression analysis.\n\nFindingsOut of 2,309 MTBC isolates, we identified 1,082 (46{middle dot}9%) single cases with 1,227 (53{middle dot}1%) isolates belonging to one of 276 clustered cases (clustering range; 2-35). Recent TB transmission rate was estimated to be 41{middle dot}2%. While we see no significant difference in the recent transmission rates between lineages of Mycobacterium africanum (lineage-5 (31{middle dot}8%); lineage-6 (24{middle dot}7%), p=0{middle dot}118), we found that lineage-4 belonging to the M. tuberculosis transmitted significantly higher (44{middle dot}9%, p<0{middle dot}001). Finally, apart from age being significantly associated with recent TB transmission (p=0{middle dot}007), we additionally identified a significant departure in the male/female ratio among very large clustered cases compared to the general TB patient population (3:1 vs. 2:1, p=0{middle dot}022).\n\nInterpretationsOur findings indicate high recent TB transmission suggesting occurrences of unsuspected outbreaks. The observed reduced transmission rate of M. africanum suggests other factor(s) may be responsible for its continuous presence in West Africa.\n\nFundingWellcome Trust Intermediate Fellowship Grant 097134/Z/11/Z to Dorothy Yeboah-Manu.

epidemiology↗

bioRxiv2017

Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests different ecological niches

Mycobacterium africanum (Maf) causes up to half of human tuberculosis in West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including both L5 and L6. We found that the genomic diversity of L6 was higher than in L5, and the selection pressures differed between both groups. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Conversely, human T cell epitopes were under purifying selection in L5, but under positive selection in L6. Although only 10% of the T cell epitopes were variable, mutations were mostly lineage-specific. Our findings indicate that Maf L5 and L6 are genomically distinct, possibly reflecting different ecological niches.

genomics↗