Publications by authors named "Fredrick Mobegi"

In the plant-plant pathosystem of rice () and the parasitic plant , cell walls from either plant are important defensive and offensive structures. Here we reveal cell wall dynamics in both and rice using simultaneous RNA sequencing. We used weighted gene co-expression network analysis (WGCNA) to home in on cell wall modification processes occurring in interactions with a resistant rice cultivar (Nipponbare) compared to a susceptible one (IAC 165).

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The advent of third-generation sequencing (TGS) represents a significant shift in the field of genetic sequencing, enabling single-molecule sequencing to overcome limitations of short-read NGS platforms. Several studies have assessed the utilisation of TGS in HLA genotyping, though many of these studies have described the high error rate as an obstacle to achieving a robust and highly accurate HLA typing assay. In 2021, Oxford Nanopore Technologies (ONT) released the high-accuracy sequencing Kit 14 and the MinION flow cell model R10.

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Chickpea (Cicer arietinum) is a pulse crop that provides an integral source of nutrition for human consumption. The close wild relatives Cicer reticulatum and Cicer echinospermum harbor untapped genetic diversity that can be exploited by chickpea breeders to improve domestic varieties. Knowledge of genomic loci that control important chickpea domestication traits will expedite the development of improved chickpea varieties derived from interspecific crosses.

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The primary goal of the HLA-DPA1 ~ promoter ~ HLA-DPB1 haplotype component of the 18th IHIWS was to characterise the extended haplotypes within the HLA-DP region and survey the extent of genetic diversity in this region across human populations. In this report, we analysed single-nucleotide polymorphisms (SNPs) in 255 subjects from 6 different cohorts. The results from the HLA-DP haplotype component have validated findings from the initial pilot study.

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Article Synopsis
  • Long-term low-dose macrolide therapy, used for chronic respiratory diseases, can alter gut microbiome composition, potentially impacting immune and metabolic regulation in the body.
  • In a study with healthy adults, low-dose erythromycin and azithromycin led to changes in gut bacteria, reducing carbohydrate metabolism ability and affecting systemic biomarkers related to immune response and metabolism.
  • The research suggests that using macrolides over a long period can significantly influence host physiology through effects on gut microbiota, emphasizing the need to understand these mechanisms to assess risks associated with prolonged therapy.
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Genetic underpinnings of host-pathogen interactions in the parasitic plant Striga hermonthica, a root parasitic plant that ravages cereals in sub-Saharan Africa, are unclear. We performed a comparative transcriptome study on five genotypes of sorghum exhibiting diverse resistance responses to S. hermonthica using weighted gene co-expression network analysis (WGCNA).

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Background: Sclerotinia sclerotiorum, the cause of Sclerotinia stem rot (SSR), is a host generalist necrotrophic fungus that can cause major yield losses in chickpea (Cicer arietinum) production. This study used RNA sequencing to conduct a time course transcriptional analysis of S. sclerotiorum gene expression during chickpea infection.

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Background: Antimicrobial resistance (AMR) represents a profound global health threat. Reducing AMR spread requires the identification of transmission pathways. The extent to which hospital wards represent a venue for substantial AMR transmission in low- and middle-income countries settings is poorly understood.

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Background: The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any patient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers.

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Poor diet and lifestyle exposures are implicated in substantial global increases in non-communicable disease burden in low-income, remote, and Indigenous communities. This observational study investigated the contribution of the fecal microbiome to influence host physiology in two Indigenous communities in the Torres Strait Islands: Mer, a remote island where a traditional diet predominates, and Waiben a more accessible island with greater access to takeaway food and alcohol. Counterintuitively, disease markers were more pronounced in Mer residents.

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The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy. To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes.

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Article Synopsis
  • LSD1 is an enzyme that decreases gene expression by removing methyl groups from histone H3, specifically lysine 4.
  • GSK2879552 and GSK-LSD1 are strong inhibitors of LSD1 that have shown promise in reducing growth in various acute myeloid leukemia cell lines.
  • Combining LSD1 inhibition with all-trans retinoic acid (ATRA) leads to enhanced anti-cancer effects, promoting differentiation and increasing toxicity against leukemia cells, with further clinical validation needed for patient treatment.
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Chronic disruption of the intestinal microbiota in adult cystic fibrosis (CF) patients is associated with local and systemic inflammation, and has been linked to the risk of serious comorbidities. Supplementation with high amylose maize starch (HAMS) might provide clinical benefit by promoting commensal bacteria and the biosynthesis of immunomodulatory metabolites. However, whether the disrupted CF gut microbiota has the capacity to utilise these substrates is not known.

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Determining the effects of antimicrobial therapies on airway microbiology at a population-level is essential. Such analysis allows, for example, surveillance of antibiotic-induced changes in pathogen prevalence, the emergence and spread of antibiotic resistance, and the transmission of multi-resistant organisms. However, current analytical strategies for understanding these processes are limited.

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Background: Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype.

Methods: The index cohort consisted of 349 patients admitted to 2 Dutch hospitals between 2000-2011 with pneumococcal bacteremia.

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East Coast fever is a lymphoproliferative disease caused by the tick-borne protozoan parasite Theileria parva. The sporozoite stage of this parasite, harboured and released from the salivary glands of the tick Rhipicephalus appendiculatus during feeding, invades and establishes infection in bovine lymphocytes. Blocking this initial stage of invasion presents a promising vaccine strategy for control of East Coast fever and can in part be achieved by targeting the major sporozoite surface protein p67.

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Campylobacter is the most common cause of foodborne bacterial illness worldwide. Faecal contamination of meat, especially chicken, during processing represents a key route of transmission to humans. There is a lack of insight into the mechanisms driving C.

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Advances in genome sequencing technologies and genome-wide association studies (GWAS) have provided unprecedented insights into the molecular basis of microbial phenotypes and enabled the identification of the underlying genetic variants in real populations. However, utilization of genome sequencing in clinical phenotyping of bacteria is challenging due to the lack of reliable and accurate approaches. Here, we report a method for predicting microbial resistance patterns using genome sequencing data.

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Unlabelled: To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality.

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The minimal subset of genes required for cellular growth, survival and viability of an organism are classified as essential genes. Knowledge of essential genes gives insight into the core structure and functioning of a cell. This might lead to more efficient antimicrobial drug discovery, to elucidation of the correlations between genotype and phenotype, and a better understanding of the minimal requirements for a (synthetic) cell.

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The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S.

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Background: Bacterial respiratory tract infections, mainly caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are among the leading causes of global mortality and morbidity. Increased resistance of these pathogens to existing antibiotics necessitates the search for novel targets to develop potent antimicrobials.

Result: Here, we report a proof of concept study for the reliable identification of potential drug targets in these human respiratory pathogens by combining high-density transposon mutagenesis, high-throughput sequencing, and integrative genomics.

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