Biology subjects

Cooksley, C.

Publications and source records attributed to Cooksley, C..

4 recordsLinked to original sources

bioRxiv2026

Genus-wide re-speciation of Corynebacterium and genomic characterisation of 87 sinus isolates resolves taxonomic conflicts and identifies four candidate novel species

Corynebacterium species are common members of the sinonasal microbiome and have shown conflicting associations with sinus health and chronic rhinosinusitis (CRS) in genus-level surveys. To better resolve the taxonomy and species-level functions of sinus corynebacteria, we generated complete long-read genome assemblies for 87 isolates, sourced from the middle meatus of 71 patients (51 with CRS, 20 healthy controls). We re-derived species boundaries de novo across the whole genus by average nucleotide identity (ANI), clustering 4,661 quality-filtered genomes retrieved from public databases and delineating higher-order species complexes. Our re-speciation assigned a species to 282 unlabelled corynebacteria, and corrected taxonomy for 266 NCBI accessions. We identified four novel candidate species from our isolate collection, and 39 public genomes fell within these species' boundaries. Whole-genome assignment reclassified 41 of our 87 isolates relative to mass-spectrometry (MALDI-TOF MS) identification, which only resolved to the species-complex level. Comparison of genome annotation characterised accessory functions that partitioned along species-complex lines, including glycogen and glycan utilisation, fatty-acid biosynthesis, cofactor (biotin and thiamine) auxotrophy, and iron-acquisition systems. Virulence and antimicrobial-resistance determinants were sparse, and the diphtheria toxin gene was universally absent. Acquired antimicrobial resistance was enriched on plasmids, whilst virulence genes were depleted from horizontally transferred compartments. Contrary to its frequent report in sinus microbiome studies, no C. tuberculostearicum genome publicly accessible via NCBI was found to be isolated from the sinonasal tract. Continued genome-level interrogation of Corynebacterium and contribution of sinus-commensals to reference databases will improve species-level understanding of the role of corynebacteria in the sinonasal microbiome.

microbiology↗

bioRxiv2023

The Intra-Host Evolutionary Landscape And Pathoadaptation Of Persistent Staphylococcus aureus In Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is a common chronic sinonasal mucosal inflammation associated with Staphylococcus aureus biofilm and relapsing infections. This study aimed to determine rates of S. aureus persistence and pathoadaptation in CRS patients by investigating the genomic relatedness and antibiotic resistance/tolerance in longitudinally collected S. aureus clinical isolates. A total of 68 S. aureus isolates were sourced from 34 CRS patients at least six months apart. Isolates were grown into 48-hour biofilms and tested for tolerance to antibiotics. A hybrid sequencing strategy was used to obtain high-quality reference-grade assemblies of all isolates. Single nucleotide variants (SNV) divergence in the core genome and sequence type clustering were used to analyse the relatedness of the isolate pairs. Single nucleotide and structural genome variations, plasmid similarity, and plasmid copy numbers between pairs were examined. Our analysis revealed that 41% (14/34 pairs) of S. aureus isolates were persisters, while 59% (20/34 pairs) were non-persisters. Persister isolates showed episode-specific mutational changes over time with a bias towards events in genes involved in adhesion to the host and mobile genetic elements such as plasmids, prophages, and insertion sequences. A significant increase in the copy number of conserved plasmids of persister strains (p<0.05) was seen, indicating a role of the "mobilome" in promoting persistence. This was accompanied by a significant increase in biofilm tolerance against all tested antibiotics (p<0.001), which was linked to a significant increase in biofilm biomass (p<0.05) over time, indicating a biofilm central pathoadaptive process in persisters. In conclusion, our study provides important insights into the mutational changes underlying S. aureus persistence in CRS patients highlighting pathoadaptive mechanisms in S. aureus persisters culminating in increased biofilm biomass linked to an increase in plasmid copy number over time.

microbiology↗

bioRxiv2019

Microbiotyping the sinonasal microbiome

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal microbiotypes or states: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

microbiology↗

bioRxiv2019

The international sinonasal microbiome study (ISMS): a multi centre, international characterization of sinonasal bacterial ecology

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterise the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus, and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. There was a significant variation in microbial diversity between countries (p = 0.001). Amongst patients suffering from CRS with nasal polyps, a significant depletion of Corynebacterium (40.29% vs 50.43%; p = 0.02) and over-representation of Streptococcus (7.21% vs 2.73%; p = 0.032) was identified. The delineation of the sinonasal microbiome and standardised methodology described within our study will enable further characterisation and translational application of the sinus microbiota.

microbiology↗