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Kwambana-Adams, B. A.

Publications and source records attributed to Kwambana-Adams, B. A..

6 recordsLinked to original sources

The global evolutionary dynamics of natural capsule switching in a human-restricted bacterial pathogen

Exchange of genetic loci encoding extracellular capsular polysaccharides in bacteria can change capsular antigens or serotype, which, in turn, can lead to evasion of vaccines targeting the capsule. However, the evolutionary dynamics and drivers of bacterial capsule switching remain poorly understood. Here, we investigate the evolutionary dynamics and correlates of capsule switching in bacteria, using the human-restricted bacterial pathogen Streptococcus pneumoniae as an example, using 10,558 genetically and geographically diverse whole-genome sequences. Our phylogenomic and ancestral state reconstruction analysis revealed that the propensity for capsule switching varies by capsule type and genetic background. We found capsule switches only between ~4% of all possible capsule-type pairs, varying by specific pairs and switching direction. We also found associations between capsule switching patterns and genetic and ecological factors, including nasopharyngeal carriage duration, capsule biosynthesis locus size, and capsule thickness. Furthermore, the genetic similarity of the replacing and replaced capsule loci was primarily associated with the frequency of switching between specific capsule type pairs. Although a few specific non-capsule genomic loci were associated with the propensity for capsule switching across distinct lineages, the collective effect of the genetic background appears to influence capsule switching more strongly. These findings shed light on how bacterial capsule types and lineages undergo capsule switching influenced by genetic and ecological factors, informing our understanding of the emergence of novel capsule-genotype combinations that may impact the design of capsule-targeting glycoconjugate vaccines.

microbiology↗

MxSure: a mixture model for inferring within-host substitution rates and transmission SNP thresholds

Quantifying short-term evolutionary rates of microbial genomes is essential for understanding the processes that shape within-host evolution and for establishing thresholds needed to track transmission. In studies of short-term evolutionary rates, samples are often collected from closely related clusters (e.g. longitudinally from the same host or from transmission pairs), with substantial time intervals separating genomes between clusters. Distinguishing strain replacement from persistence presents is also difficult in these studies. In addition, many public health and metagenomic bacterial strain tracking pipelines output pairwise SNP distances rather than the multiple sequence alignments required by common substitution rate estimation pipelines. This makes it hard to estimate within-host evolutionary rates in many commensal bacterial species that are difficult to culture and isolate. To address these challenges, we introduce MxSure, a tool for estimating substitution rates and transmission thresholds while accounting for strain replacement from pairwise SNP distance data, as commonly generated by transmission tracking and metagenomic analysis pipelines. We demonstrate the accuracy of MxSure through extensive simulations and by analysing species with previously estimated substitution rates from longitudinal metagenomic datasets. Using MxSure, we estimated within-host substitution rates and transmission SNP thresholds for multiple commensal bacterial species including Bifidobacterium longum and Bifidobacterium bifidum from a longitudinal study of the infant gut microbiome.

bioinformatics↗

Genomic diversity and antimicrobial resistance among non-typhoidal Salmonella associated with human disease in The Gambia

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan African. Specific lineages of serovars S. Typhimurium and S. Enteritidis are implicated. We characterised the genomic diversity of 100 clinical Non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern and 2006 to 2018 in the western regions of The Gambia respectively. Phenotypic susceptibility applied Kirby Baur disk diffusion and whole genome sequencing utilized Illumina platforms. The predominant serovars were S. Typhimurium ST19 (31/100) and S. Enteritidis ST11 (18/100) restricted to invasive disease with the notable absence of S. Typhimurium ST313. Phylogenetic analysis performed in the context of 495 African strains from the European Nucleotide Archive confirmed the presence of the S. Enteritidis virulent epidemic invasive multidrug resistant West African clade. Multidrug resistance including chloramphenicol and azithromycin has emerged among the West African S. Enteritidis clade 7/9 (78%) with potential for spread, thus having important implications for patient management warranting systematic surveillance and epidemiologic investigations to inform control. Data summarySequences are deposited in the NCBI sequence reads archive (SRA) under BioProject ID:PRJEB38968. The genomic assemblies are available for download from the European Nucleotide Archive (ENA): http://www.ebi.ac.uk/ena/data/view/. Accession numbers SAMEA6991082 to SAME6991180

genomics↗

Genomic diversity of Escherichia coli isolates from backyard chickens and guinea fowl in the Gambia

Chickens and guinea fowl are commonly reared in Gambian homes as affordable sources of protein. Using standard microbiological techniques, we obtained 68 caecal isolates of Escherichia coli from ten chickens and nine guinea fowl in rural Gambia. After Illumina whole-genome sequencing, 28 sequence types were detected in the isolates (four of them novel), of which ST155 was the most common (22/68, 32%). These strains span four of the eight main phylogroups of E. coli, with phylogroups B1 and A being most prevalent. Nearly a third of the isolates harboured at least one antimicrobial resistance gene, while most of the ST155 isolates (14/22, 64%) encoded resistance to [≥]3 classes of clinically relevant antibiotics, as well as putative virulence factors, suggesting pathogenic potential in humans. Furthermore, hierarchical clustering revealed that several Gambian poultry strains were closely related to isolates from humans. Although the ST155 lineage is common in poultry from Africa and South America, the Gambian ST155 isolates belong to a unique cgMLST cluster comprised of closely related (38-39 alleles differences) isolates from poultry and livestock from sub-Saharan Africa--suggesting that strains can be exchanged between poultry and livestock in this setting. Continued surveillance of E. coli and other potential pathogens in rural backyard poultry from sub-Saharan Africa is warranted. Author notesAll supporting data and protocols have been provided within the article or as supplementary data files. Eleven supplementary figures and eight supplementary files are available with the online version of this article. Data summaryThe genomic assemblies for the isolates reported here are available for download from EnteroBase (http://enterobase.warwick.ac.uk/species/index/ecoli) and the EnteroBase assembly barcodes are provided in File S2. Sequences have been deposited in the NCBI SRA, under the BioProject ID: PRJNA616250 and accession numbers SAMN14485281 to SAMN14485348 (File S2). Assemblies have been deposited in GenBank under the BioProject ID: PRJNA616250 and accession numbers CP053258 and CP053259. Impact statementDomestic birds play a crucial role in human society, in particular contributing to food security in low-income countries. Many households in Sub-Saharan Africa rear free-range chickens and guinea fowl, which are often left to scavenge for feed in and around the family compound, where they are frequently exposed to humans, other animals and the environment. Such proximity between backyard poultry and humans is likely to facilitate transmission of pathogens such as Escherichia coli or antimicrobial resistance between the two host species. Little is known about the population structure of E. coli in rural chickens and guinea fowl, although this information is needed to contextualise the potential risks of transmission of bacterial strains between humans and rural backyard poultry. Thus, we sought to investigate the genomic diversity of E. coli in backyard poultry from rural Gambia.

genomics↗

Within-Host Diversity and Vertical Transmission of Group B Streptococcus Among Mother-infant Dyads in The Gambia

IntroductionUnderstanding mother-to-infant transmission of Group B Streptococcus (GBS) is vital to the prevention and control of GBS disease. We investigated the transmission and phylogenetic relationships of mothers colonised by GBS and their infants in a peri-urban setting in The Gambia.\n\nMethodsWe collected nasopharyngeal swabs from 35 mother-infant dyads at weekly intervals from birth until six weeks post-partum. GBS was isolated by conventional microbiology techniques. Whole-genome sequencing was performed on GBS isolates from one mother-infant dyad (dyad 17).\n\nResultsWe recovered 85 GBS isolates from the 245 nasopharyngeal swabs. GBS was isolated from 16.33% and 18.37% of sampled mothers and infants, respectively. In 87% of cultured swabs, the culture status of an infant agreed with that of the mother (Kappa p-value <0.001). In dyad 17, phylogenetic analysis revealed within-host strain diversity in the mother and clone to her infant.\n\nConclusionGBS colonisation in mothers presents a significant risk of colonisation in their infants. We confirm vertical transmission from mother to child in dyad 17, accompanied by within-host diversity.

microbiology↗

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the United States, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identify a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.\n\nAuthor SummaryStreptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data form 301 isolates collected among 24 countries from 1993-2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need to routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.

evolutionary biology↗