Biology subjects

Makaranga, A.

Publications and source records attributed to Makaranga, A..

5 recordsLinked to original sources

bioRxiv2026

Restrictome-EVOLVE: population-resolved haplotype architecture of human antiviral restriction-factor loci

Human antiviral restriction factors act across multiple stages of viral replication, but whether their population-resolved haplotype architecture differs systematically from comparable genomic regions is unclear. We tested this using phased public human genomic data from 660 individuals in seven African and African-diaspora populations, representing 30 canonical restriction-factor units and 436 target windows. Each canonical unit was compared with 80 exact matched genomic controls, yielding 2,400 frozen controls and 4,429,760 target-control endpoint comparisons across 19 retained haplotype endpoints. All 30 canonical units showed lower differentiation effects and lower robust population-private haplotype effects than their matched controls. Within-population diversity effects were higher in 19 of 30 units, whereas dominant-haplotype concentration effects were lower in 22 of 30. Nineteen units occupied a deconcentrated/high-diversity state, eight a concentrated/low-diversity state, and three a lower-diversity/lower-concentration state. Of 127 global endpoint/context summaries, 88 reached a global false-discovery-rate q value below 0.05; 76 were lower in restriction-factor targets and 12 were higher. Directional sign-test inference detected widespread repeated displacement relative to matched controls, whereas no matched-cell empirical-rank test reached global false-discovery-rate significance. These results show that human antiviral restriction-factor loci occupy a reproducible matched-control haplotype architecture characterized by attenuated population partitioning and reduced robust private structure, together with substantial locus-specific variation in within-population diversity and haplotype concentration. The comparative framework separates population-genomic structure from claims of functional or adaptive causality.

bioinformatics↗

bioRxiv2026

Genome-resolved surveillance of African Klebsiella oxytoca species complex genomes reveals resistome-mobilome and biosynthetic gene cluster diversity

The Klebsiella oxytoca species complex (KoSC) comprises taxonomically diverse commensals and opportunistic pathogens, but its genomic diversity remains poorly characterized across Africa. We curated publicly available African KoSC data through raw-read and public-assembly routes and analyzed 163 African genomes together with 282 global comparators. Pangenome, phylogenomic, sequence-typing, surface-locus, antimicrobial-resistance, plasmid-replicon, mobile-element, biosynthetic-gene-cluster, and virulence-component analyses were integrated. The African collection comprised K. michiganensis (112/163), K. oxytoca (36/163), K. pasteurii (8/163), and K. grimontii (7/163) from 13 countries. The African pangenome contained 4,286 core, 4,505 shell, and 18,066 cloud gene families. Official PubMLST sequence types were assigned to 129/163 genomes. Four core/intrinsic antimicrobial-resistance-associated loci (ompA, oqxA, oqxB, and blaOXY) occurred in all genomes, whereas acquired resistance determinants were heterogeneous. Intact til biosynthetic gene clusters occurred in 55/163 genomes and intact leup clusters in 103/163. leup was concentrated in K. michiganensis (102/112), whereas intact til was frequent in K. oxytoca (26/36), K. pasteurii (7/8), and K. grimontii (7/7). Klebsiella-focused Virulence Factor Database screening detected at least one curated component in 112/163 genomes, but no complete curated factor; three K. michiganensis genomes carried complete mrkABCDF structural-operon candidates. These data define an African genome-resolved baseline for KoSC diversity and identify species-structured biosynthetic loci alongside heterogeneous resistance and mobilome profiles.

microbiology↗

bioRxiv2026

Host breadth, genomic exchange and antimicrobial-resistance evolution in East African Campylobacter

Campylobacter jejuni and Campylobacter coli occupy diverse animal reservoirs, yet the genomic processes associated with variation in host breadth remain poorly resolved in East Africa. Publicly available isolate-level whole-genome sequencing data from Ethiopia, Kenya, Tanzania and Uganda were analysed using a standardized population-genomic workflow. After genome reconstruction, species confirmation and quality filtering, 722 genomes were retained, comprising 586 C. jejuni and 136 C. coli. Animal-host breadth among sufficiently represented Ethiopian C. jejuni lineages was standardized by exact rarefaction across chicken, cattle, goat and sheep hosts. Fifteen lineages were eligible for discovery analyses. Host breadth showed no detectable association with homologous recombination, accessory-genome fluidity, human representation, antimicrobial-resistance class burden, recurrent AMR evolution or regional recurrence. Six discovery lineages recurred outside Ethiopia, but only one occurred in at least two validation countries, and validation animal sampling was insufficient for inferential replication of host-breadth or AMR associations. Recurrent within-lineage AMR evolution was restricted to a small number of determinants, lineage combinations involving tet(O) and gyrA T86I. Analysis of complete single-copy loci identified a restricted set of strongly supported cross-species placements, providing evidence consistent with localized interspecies introgression without implying whole-genome admixture or transfer direction. These findings indicate that animal-host breadth in regional C. jejuni populations is not explained by simple lineage-wide measures of genome exchange, human occurrence or AMR burden, but instead reflects lineage-specific combinations of ecological opportunity, selected genomic variation and population history.

evolutionary biology↗

bioRxiv2026

African Campylobacter jejuni genomes reveal globally connected population structure and regionally variable resistance, virulence and mobilome profiles

Campylobacter jejuni is a leading foodborne cause of gastroenteritis, but genomic surveillance remains uneven across Africa. A recent East Africa study combined whole-genome sequencing and antimicrobial susceptibility testing for Campylobacter isolates from humans with diarrhea in Kenya and poultry in Tanzania, showing high sequence-type diversity and substantially higher multidrug resistance in poultry. We extended this regional evidence by analyzing 1,013 publicly available C. jejuni genomes, including 718 African and 295 non-African comparator genomes, with standardized assembly, genotyping, phylogenomics, pangenome reconstruction, antimicrobial resistance, virulence, and mobile-element profiling. African genomes were geographically concentrated but genetically diverse, included globally distributed and regionally enriched lineages, and showed an open pangenome dominated by low-frequency gene families. Resistance and virulence determinants were unevenly distributed by region and lineage. These findings place African C. jejuni diversity within a global evolutionary framework and support expanded, integrated One Health genomic surveillance. Data summaryAll genome sequence data analysed in this study were retrieved from publicly accessible repositories, including the National Center for Biotechnology Information Sequence Read Archive and Assembly resources and corresponding records available through the International Nucleotide Sequence Database Collaboration where applicable. Accession identifiers, BioSample records, run accessions, country metadata and host/source information for all analysed genomes are provided in the combined Supplementary Data workbook. No new sequence data were generated. The analysis used publicly available data generated by other investigators, and the original data-generating studies are cited where appropriate. Derived analytical outputs supporting the findings are included in the manuscript and Supplementary Information. Impact statementGenomic surveillance of Campylobacter jejuni remains uneven globally, and African data are still underrepresented in many comparative analyses. This study brings together publicly available African and non-African C. jejuni genomes in a single standardized comparative framework, linking population structure, pangenome composition, antimicrobial-resistance determinants, virulence-associated loci and mobile-element profiles. The work shows that African C. jejuni diversity is not peripheral to the global population: African genomes include globally distributed sequence types, regionally enriched lineages and a large accessory-gene repertoire. By separating genomic surveillance signals from population-representative prevalence claims, the study provides a cautious framework for interpreting public genome collections from settings with unequal sampling. The findings support broader One Health genomic surveillance, improved metadata completeness and geographically balanced sequencing to better understand foodborne transmission, resistance evolution and lineage diversification in this important zoonotic pathogen.

microbiology↗

bioRxiv2025

Phage metagenome assembled genomes portraying anti-ESKAPE and anti CRISPR/Cas potential; datasets from sewage clinical settings of Western Uganda, subSaharan Africa

ESKAPE pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., which account for the major causes of mortality linked to the spread of infection and antimicrobial resistance (AMR) globally. Advances in omics approaches have pointed to bacteriophages as a promising alternative source of antibacterial agents. Here we enriched two samples from sewage and amplified them on Staphylococcus culture, followed by whole metagenome shotgun sequencing with Illumina NovaSe X. We performed metagenomic classification of high-quality sequence reads using the Kraken 2 database, to delineate the diversity and abundances of taxa. Thereafter we assembled the sequence reads with MAGAHIT and binned them with default parameters of the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) before annotating each bin with PhageScope. From assembly, we recovered multiple metagenome-assembled genomes (MAGs) including Alistipes phage, Escherichia phage, Vibrio phage, Staphylococcus phage, Klebsiella phage and Acinetobacter phage, to mention the top six best hits. From annotation, while the Acinetobacter phage is virulent, the two Klebsiella phage and Staphylococcus phage are temperate. All the phages possess more than four lysis genes, with the potential to disrupt bacterial membranes. Exceptionally, Vibrio phage, Acinetobacter phage and Alistipes phage possess anti-CRISPR genes, the potential to counteract normal bacterial immune response to phage infection. These findings also inform that MAGs from the sewage have the potential to recover phages with anti-CRISPR/Cas activity, which is one of the desirable attributes for effective phage-bacterial infection to control the growth and multiplication of bacteria. Our datasets can be utilized for genome-guided selection of potent phages through lytic and host-range assays, towards the purification of endolysins (lysozymes) as alternative antibacterial agents. VALUE OF THE DATAO_LIMetagenome-assembled genomes (MAGs) of lytic phages could present a potential model to combat multidrug-resistant Staphylococcus, Klebsiella and Acinetobacter species, which are WHOs high-priority pathogens. C_LIO_LIPhages with bacterial infective potential can be used as model gene vehicles and vectors for gene and genome editing studies as they possess hydrolytic enzymes targeting the bacterial cell walls, chromosomal DNA sequences and anti-CRISPR/Cas proteins. C_LIO_LIComparing raw and processed datasets, MAGs provide an avenue for the pursuit of novel industrial strains from local resources in East Africa. C_LI

genomics↗