Biology subjects

Nicol, M. P.

Publications and source records attributed to Nicol, M. P..

6 recordsLinked to original sources

bioRxiv2026

Upper respiratory tract bacterial microbiome features associated with Streptococcus pneumoniae colonisation, environmental and demographic factors among older children in a rural setting in The Gambia

Abstract The upper respiratory tract (URT) microbiome plays a vital role in respiratory health, with older children (5-14 years old) serving as key reservoirs for the transmission of bacteria to younger individuals (< 5 years old). However, the URT microbiome in this age group remains poorly characterised, particularly in relation to colonisation by the pathobiont Streptococcus pneumoniae. To address this gap, we analysed URT samples collected over eight visits from 134 healthy children aged 5-14 years in The Gambia, using culture-dependent methods to detect S. pneumoniae and culture-independent 16S rRNA sequencing to characterise the microbiome in parallel. 16S rRNA sequencing identified Streptococcus and Prevotella as the dominant microbiome constituents. When integrating longitudinal sampling data, we observed temporal instability with frequent switches in microbiome profiles over time. URT samples colonised with S. pneumoniae were associated with increased abundance of Moraxella, Streptococcus and Haemophilus, whereas non-colonised URT samples were enriched with Granulicatella and Filifactor. S. pneumoniae colonisation was also associated with lower Shannon diversity compared with non-colonised samples. Age and season were the strongest determinants of microbiome composition; increasing age was associated with decreasing prevalence and abundance of taxa including Haemophilus and Moraxella, while gram-positive taxa were predominantly enriched in the dry season. These findings provide new insight into the URT microbiome of older children in The Gambia and highlight Granulicatella and Filifactor as potential contributors to colonisation resistance against S. pneumoniae.

microbiology↗

bioRxiv2025

Immune transcriptomic differences in paediatric patients with SARS-CoV-2 compared to other lower respiratory tract infections

The clinical severity of SARS-CoV-2 infection in children varies, with asymptomatic or mild illness predominating and a minority developing severe disease. Understanding the immunological responses that underlie severity of disease may guide future development of preventive or therapeutic interventions. This study compared whole blood transcriptomes of healthy children (N=127), children with mild/asymptomatic SARS-CoV-2 infection (N=71) and children hospitalised with severe SARS-COV-2 (N=41), lower respiratory tract illness (LRTI) or LRTI due to Respiratory Syncytial Virus (RSV-LRTI) (N=47) or Pulmonary Tuberculosis (PTB) (N=47). We identified >5000 differentially expressed genes including: OLFM4, IFI27, CBX7, IGF2BP3, OTOF for severe SARS-CoV-2; IFI27, OTOF, SIGLEC1, IFI44L and USP18 for RSV-LRTI, and MMP8, LTF, IGF2BP3, GPR84, CD177, C1QC and DEFA4 for PTB, at false discovery rate (FDR) <0.05. Pathway analysis identified enrichment for neutrophil degranulation, interferon gamma signalling, overexpression of ribosomal proteins and depletion of immune response in severe SARS-CoV-2 compared to healthy (SAR-COV-2 uninfected) children. Weighted Gene Co-expression Network Analysis (WGCNA) identified 10 correlated gene modules shared between LRTI showing similar underlying response mechanisms. Cellular decomposition analysis identified the depletion of 22 cell types in severe SARS-CoV-2, 16 for RSV-LRTI and 21 for PTB compared to healthy SARS-CoV-2 uninfected control children. We identified 82 genes important for discriminating asymptomatic/mild from severe SARS-CoV-2 including CBX7, TRAF1, ZNF324 and CASS4; 93 healthy from severe SARS-CoV-2 including RORC, CBX7, NR3C2, MID2 and ADAMTS2; 110 genes for RSV-LRTI and 95 for PTB children which can be used for future therapeutic targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/687132v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@13db618org.highwire.dtl.DTLVardef@7df9e2org.highwire.dtl.DTLVardef@a0a448org.highwire.dtl.DTLVardef@818cef_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Characterisation of Ornithobacterium hominis colonisation dynamics and interaction with the nasopharyngeal microbiome in a South African birth cohort.

Ornithobacterium hominis is a recently described Gram-negative bacterium that colonises the human nasopharynx and may be associated with poor upper respiratory tract health. Here, we describe the isolation of O. hominis from samples collected from a South African birth cohort, creating the first archive of cultured strains of the species from Africa. Sequenced genomes from this archive reveal that South African O. hominis is more similar to Australian strains than those from Southeast Asia, and that it may share genes with other members of the microbiome that are relevant for virulence, colonisation, and antibiotic resistance. Leveraging existing microbiome data from the cohort, O. hominis was found to be closely associated with bacterial co-colonisers that are rare in non-carrier individuals, including Suttonella, Helcococcus, Moraxella spp., and Gracilibacteria. Their collective acquisition has a significant impact on the diversity of nasopharyngeal communities that contain O. hominis. Individuals who have not yet acquired O. hominis have a higher abundance of Moraxella (particularly M. lincolnii) than individuals who never acquire O. hominis, suggesting that this could be a precursor state for successful colonisation. Finally, a novel co-coloniser species, Helcococcus ekapensis, was successfully isolated and sequenced. Data SummaryOrnithobacterium hominis data have been deposited under project accession ERP149886. This comprises genome sequences for isolates SA-OH-C1 (ERR13967269), SA-OH-C2 (ERR13967270), SA-OH-C3 (ERR13967271), SA-OH-C4 (ERR13967272, ERR13967275), SA-OH-C5 (ERR13967273), SA-OH-C6 (ERR13967274, ERR13967276). Previously published 16S rRNA gene data are deposited under project accessions PRJNA790843 and PRJNA548658. Helcococcus ekapensis genome data are deposited under project accession PRJEB85661. Software usedO_LIAMRFinderPlus v3.12.8: https://github.com/ncbi/amr C_LIO_LIAssembleBAC-ONT v1.1.1: https://github.com/avantonder/assembleBAC-ONT C_LIO_LIBAKTA v1.8.1: https://bakta.computational.bio/ C_LIO_LIBLAST v2.16.0: https://blast.ncbi.nlm.nih.gov/Blast.cgi C_LIO_LIComprehensive Antibiotic Resistance Database (CARD) Resistance Gene Identifier (RGI) tool v1.2.1: https://card.mcmaster.ca/analyze/rgi C_LIO_LIDecontam v1.12 (R package): https://github.com/benjjneb/decontam C_LIO_LIEggnog-mapper v2.0.1: http://eggnog-mapper.embl.de/ C_LIO_LIFastANI v1.1.0: https://github.com/ParBLiSS/FastANI C_LIO_LIFlye v2.9.2: https://github.com/fenderglass/Flye C_LIO_LIGuppy v6.5.7: https://community.nanoporetech.com/downloads/guppy/release_notes C_LIO_LIISEScan v1.7.2.3: https://usegalaxy.eu/root?tool_id=toolshed.g2.bx.psu.edu/repos/iuc/isescan/isescan/1.7.2.3+galaxy1 C_LIO_LIMedaka v1.9.1: https://github.com/nanoporetech/medaka C_LIO_LIMEGA11: https://www.megasoftware.net/ C_LIO_LIMMseqs2 v17: https://github.com/soedinglab/MMseqs2 C_LIO_LIMothur v1.44.3: https://github.com/mothur/mothur C_LIO_LINetCoMi v1.2.0 (R package): https://github.com/stefpeschel/NetCoMi C_LIO_LIPanaroo v1.4.3: https://github.com/gtonkinhill/panaroo C_LIO_LIPHASTEST: https://phastest.ca/submissions/new C_LIO_LIProwler (commit ID c3041ba): https://github.com/ProwlerForNanopore/ProwlerTrimmer C_LIO_LIR v4.4.3: https://www.r-project.org/ C_LI Databases usedO_LIComprehensive Antibiotic Resistance Database (CARD): https://card.mcmaster.ca/ C_LIO_LIEuropean Nucleotide Archive: https://www.ebi.ac.uk/ena/ C_LIO_LIGenome Taxonomy Database (GTDB) release 09-RS220: https://gtdb.ecogenomic.org/ C_LIO_LIRefSeq release 228: https://www.ncbi.nlm.nih.gov/refseq/about/prokaryotes/ C_LIO_LISILVA v132: https://www.arb-silva.de/ C_LI Impact statementFirst described in 2019, Ornithobacterium hominis is an understudied bacterium that may be associated with poor respiratory health in children. The study builds upon existing knowledge of O. hominis by describing the first African isolates of the species, its potential as a reservoir of virulence and antibiotic resistance genes in the upper respiratory tract, and the unique microbiome profile of O. hominis carriers.

microbiology↗

bioRxiv2025

Understanding the population structure of Moraxella catarrhalis using core genome multilocus sequence typing (cgMLST) and a life identification number (LIN) code classification system

Moraxella catarrhalis is an important cause of infectious exacerbations of chronic obstructive pulmonary disease and otitis media. Previously, seroresistant (SR) and serosensitive (SS) lineages that differed in virulence potential were described, which raised questions about their evolutionary relationship and species classification. To investigate the population structure of M. catarrhalis, we developed a core-genome multilocus sequence typing (cgMLST) scheme using 1,319 core genes, and a life identification number (LIN) barcode classification system. Whole-genome analyses of nearly 2,000 genomes confirmed two divergent SR and SS M. catarrhalis lineages with distinct evolutionary trajectories. SR genomes were more conserved, while SS genomes exhibited greater genetic variability. Virulence gene analyses revealed lineage-specific variations in ubiquitous surface proteins (UspA1 and UspA2) and lipooligosaccharide (LOS) types, and SR genomes had more diverse LOS variants. The bro {beta}-lactamase gene, and the mcb bacteriocin cluster, were more common in SR, which suggested different selective pressures and ecological adaptation. This cgMLST scheme and LIN code system provides a robust method for characterising M. catarrhalis, distinguishes between SR and SS lineages, and offers a unified framework for population structure analyses. Implemented within PubMLST, this open-access resource facilitates high-resolution genomic studies and supports the scientific community in understanding the evolutionary complexity of M. catarrhalis.

genomics↗

bioRxiv2023

Evidence of virulence and antimicrobial resistance in Streptococcus pneumoniae serotype 16F lineages

IntroductionDue to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). AimTo characterise lineages and antimicrobial resistance in 16F isolates obtained from South Africa and placed the local findings in a global context. MethodologyWe analysed 10923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and Global Pneumococcal Sequence Clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19,607, collected from 49 countries across five continents, years covered (1995 - 2018), accessed on 17th March 2022). ResultsNine percent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2% (419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26% (346/1353) and 53% (716/1353), respectively. Serotype 16F isolates were identified globally, however, most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95% CI) 0.24 (0.09 - 0.66); p=0.003], while GPSC46 was associated with disease [OR (95% CI) 19.9 (2.56 - 906.50); p=0.0004]. 10% (37/346) and 15% (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18% (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters which may suggest emerging resistant lineages. DiscussionSerotype 16F lineages are common in Southern Africa. Some of these lineages are associated with disease, and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine long term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. DATA SUMMARYThe sequencing reads for the genomes analysed have been deposited in the European Nucleotide Archive and the accession numbers for each isolate are listed in Supplementary Table1. Phylogenetic tree of serotype 16F pneumococcal genomes and associated metadata are available for download and visualisation on the Microreact website: Phylogenies of seotype 16F, GPSC33 and GPSC46 are available on the Microreact serotype-16F, GPSC33 and GPSC46, respectively. IMPACT STATEMENTThis study shows that serotype 16F lineages are predominant in Southern Africa and are associated with disease and antimicrobial resistance. Although serotype 16F has been included in the newer formulation of the upcoming vaccine formulations of PCV21 and IVT-25, continuous surveillance to determine long term impact of serotype 16F lineages on vaccines and antimicrobial therapy remains essential.

genomics↗

bioRxiv2019

Association of maternal prenatal psychological stressors and distress with maternal and early infant faecal bacterial profile

BackgroundFindings from animal studies indicate that the early gut bacteriome is a potential mechanism linking maternal prenatal stress with health trajectories in offspring. However, clinical studies are scarce and the associations of maternal psychological profiles with the early infant faecal bacteriome is unknown. This study aimed to investigate the associations of prenatal stressors and distress with early infant faecal bacterial profiles in a South African birth cohort study.\n\nMethodsAssociations between prenatal symptoms of depression, distress, intimate partner violence (IPV) and posttraumatic stress-disorder (PTSD) and faecal bacterial profiles were evaluated in meconium and subsequent stool specimens from 84 mothers and 101 infants at birth, and longitudinally from a subset of 69 and 36 infants at 4-12 and 20-28 weeks of age, respectively in a South African birth cohort study.\n\nResultsInfants born to mothers exposed to high levels of IPV had significantly higher proportions of unclassified genera within the family Enterobacteriaceae detected at birth; higher proportions of the genus Weissella at 4-12 weeks; and increased proportions of genera within the family Enterobacteriaceae over time (birth to 28 weeks of life). Faecal specimens from mothers exposed to IPV had higher proportions of the family Lactobacillaceae and lower proportions of Peptostreptococcaceae at birth. Maternal psychological distress was associated with decreased proportions of the family Veillonellaceae in infants at 20-28 weeks and a slower decline in Gammaproteobacteria over time. No changes in beta diversity were apparent for maternal or infant faecal bacterial profiles in relation to any of the prenatal measures for psychological adversities.\n\nConclusionIPV during pregnancy is associated with altered bacterial profiles in infant and maternal faecal bacteria. These findings may provide insights in the involvement of the gut bacteria linking maternal psychological adversity and the maturing infant brain.

neuroscience↗