Biology subjects

Timms, V. J.

Publications and source records attributed to Timms, V. J..

6 recordsLinked to original sources

bioRxiv2026

Markers of biosynthetic innovation in the Cyanobacteria

Cyanobacteria are a rich source of specialised metabolites of ecological, biomedical and industrial significance, yet discovery of novel compounds is constrained by rediscovery and uneven taxonomic exploration. Diversification of specialised metabolism constitutes a key evolutionary innovation associated with ecological expansion. Further, understanding how biosynthetic capacity is distributed across cyanobacterial lineages and environments is critical for guiding natural product discovery. We therefore analysed 939 cyanobacterial genomes spanning 11 orders and five habitat types to identify taxonomic and ecological hotspots of biosynthetic potential. We evaluated several indicators of biosynthetic innovation, including singleton BGCs and specialized enzymes and assessed the distribution of cyanobacterial toxin BGCs. Conserved terpene and ribosomally synthesised and post-translationally modified peptide (RiPP) clusters dominated, accounting for >50% of identified BGCs. These two classes exhibited high sequence conservation, averaging 16.41 and 28.10 similarity links per BGC, respectively. Conversely, NRPS and polyketide synthase clusters were less common (18.5% and 2.5% of total BGCs, respectively) but displayed considerable sequence diversity, with a mean of 1.9 and 0.79 links per BGC, respectively. Enzymes associated with potentially novel chemistries were rare, with halogenases and cytochrome P450s present in 4.9% and 1.27% of BGCs, respectively, whereas amidinotransferases were detected in only 0.42% of BGCs. Symbiotic, terrestrial and thermal spring cyanobacteria, particularly Nostocales, showed elevated biosynthetic potential, whereas marine Synechococcales genomes showed comparatively low biosynthetic potential. Putative toxin BGCs were enriched in freshwater Nostocales, Chroococcales and Oscillatoriales. These findings link phylogeny, ecology and genomic features to prioritise taxa, habitats and biosynthetic pathways for future natural product discovery.

genomics↗

bioRxiv2026

Comparative genomics of Dolichospermum circinale strains with differential paralytic shellfish toxin profiles

The cyanobacterium Dolichospermum circinale is a known producer of the neurotoxin saxitoxin and its analogues, collectively known as the paralytic shellfish toxins (PSTs). PSTs vary in potency, and the reported toxin profiles of D. circinale blooms vary in the quantities of individual PSTs, with the regulation of these profiles being poorly understood. In this study, we present the genomes of four D. circinale strains (ACBU01, ACMB03, ACMB13 and FSS-124) with unique PST profiles and perform genome-wide comparisons and specific analysis of the PST-producing biosynthetic gene cluster (sxt) to understand the variability in PST quotas. A reassessment of the previously published D. circinale AWQC131C genome was also performed to collate genomic variation between all strains. Analysis at the nucleotide and amino acid sequence level revealed that toxic strains maintain high genome-wide similarities, corroborated by the analysis of the pan- and variable genomes of each strain. Specifically, the sxt gene sequences were 99-100% identical across all strains. Novel tailoring (sxtSUL, sxtDIOX) and transport (sxtM4) genes were identified within the sxt cluster that were not reported previously in D. circinale. Taken together, these results indicate that the genetic machinery involved in PST production is conserved in this species, suggesting that the regulation of PST biosynthesis in D. circinale does not occur at the genomic level.

microbiology↗

bioRxiv2022

Can genomics and meteorology predict outbreaks of legionellosis in urban settings?

Legionella pneumophila is ubiquitous and sporadically infects humans causing Legionnaires disease (LD). Globally, reported cases of LD has risen four-fold from 2000-2014. In 2016, Sydney, Australia was the epicentre of an outbreak caused by L. pneumophila serogroup 1 (Lpsg1). Whole genome sequencing was instrumental in identifying the causal clone which was found in multiple locations across the city. This study examined the epidemiology of Lpsg1 in an urban environment, assessed typing schemes to classify resident clones and investigated the association between local climate variables and LD outbreaks. Of 223 local Lpsg1 isolates, we identified dominant clones with one clone isolated from patients in high frequency during outbreak investigations. The cgMLST scheme was the most reliable in identifying this Lpsg1 clone. While an increase in humidity and rainfall was found to coincide with a rise in LD cases, the incidence of the major L. pneumophila outbreak clone did not link to weather phenomena. These findings demonstrated the role of high resolution typing and weather context assessment in determining source attribution for LD outbreaks in urban settings, particularly when clinical isolates remain scarce. ImportanceWe investigated the genomic and meteorological influences of infections caused by Legionella pneumophila in Sydney, Australia. Our study contributes to a knowledge gap of factors that drive outbreaks of legionellosis compared to sporadic infections in urban settings. In such cases, clinical isolates can be rare and other data is then relied upon to inform decision making around control measures. We found that cgMLST typing offered a robust and scalable approach for high-resolution investigation of Lpsg1 outbreaks. The genomic landscape of Lpsg1 in Sydney was dominated by a single clone which was responsible for multiple clusters of community cases over four decades. While legionellosis incidence peaked in Autumn, this was not linked to the dominant outbreak clone. The synthesis of meteorological data with Lpsg1 genomics can be a part of the risk assessment for legionellosis in urban settings and is relevant for other densely populated areas around the world.

microbiology↗

bioRxiv2019

Complete microbial genomes for public health in Australia and Southwest Pacific

Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health lab activities. Here, we present complete genomes of pathogen strains of regional importance to the Southwest Pacific and Australia. These enrich the catalogue of globally available complete genomes for public health while providing valuable strains to regional public health labs.\n\nAnnouncementWhole-genome sequence (WGS) data is increasingly important in public health microbiology (1-4). The data can be used to replicate many of the basic bacterial sub-typing approaches, as well as support epidemiological investigations, such as surveillance and outbreak investigation (5-7). The appeal of WGS data comes from the promise of a single workflow to process all microbial pathogens that can provide easily portable data that promotes deeper integration of surveillance and investigation efforts across jurisdictions. This promise is leading to a concerted effort to move microbial public health to a primarily genome-based workflow at numerous jurisdictions (8-10), including Australia (11).

genomics↗

bioRxiv2017

Genome Sequencing Links Persistent Outbreak Of Legionellosis In Sydney To An Emerging Clone Of Legionella pneumophila ST211

The city of Sydney, Australia, experienced a persistent outbreak of Legionella pneumophila serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and bring the outbreak to a close we examined the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks. A total of 48 isolates from patients and cooling towers were sequenced and compared using SNP-based, core-genome MLST and pangenome approaches. All three methods confirmed phylogenetic relatedness between isolates associated with outbreaks in the Central Business District (March and May) and Suburb 1. These isolates were designated \"Main cluster\" and consisted of isolates from two patients from the CBD March outbreak, one patient and one tower isolate from Suburb 1 and isolates from two cooling towers and three patients from the CDB May outbreak. All main cluster isolates were sequence type ST211 which has only ever been reported in Canada. Significantly, pangenome analysis identified mobile genetic elements containing a unique T4ASS that was specific to the main cluster and co-circulating clinical strains, suggesting a potential mechanism for increased fitness and persistence of the outbreak clone. Genome sequencing was key in deciphering the environmental sources of infection among the spatially and temporally coinciding cases of legionellosis in this highly populated urban setting. Further, the discovery of a unique T4ASS emphasises the potential contribution of genome recombination in the emergence of successful Lp1 clones.

genomics↗

bioRxiv2017

Genome-Wide Comparison Of Toxigenic And Non-Toxigenic Corynebacterium diphtheriae Isolates Identifies Differences In The Pan Genomes Between Respiratory And Cutaneous Strains

ObjectivesCorynebacterium diphtheriae is the main etiological agent of diphtheria, a global disease causing life-threatening infections, particularly in infants and children. Vaccination with diphtheria toxoid protects against infection with potent toxin producing strains. However a growing number of apparently non-toxigenic but potentially invasive C. diphtheriae strains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species.\n\nMethodsThis study examined genomic diversity among 47 C. diphtheriae isolates collected in Australia over a 10-year period using whole genome sequencing. Phylogeny was determined using SNP-based mapping and genome wide analysis.\n\nResultsC. diphtheriae sequence type (ST) 32, a non-toxigenic ST with evidence of enhanced virulence that is also circulating in Europe, appears to be endemic in Australia. Isolates from temporospatially related patients displayed the same ST and similarity in their core genomes. The genome-wide analysis highlighted a role of pilins, adhesion factors and iron utilization in infections caused by toxigenic as well as non-toxigenic strains.\n\nConclusionsThe genomic diversity of toxigenic and non-toxigenic strains of C. diphtheriae in Australia suggests multiple local and overseas sources of infection and colonisation. Our findings suggest that regular genomic surveillance of co-circulating toxigenic and non-toxigenic C. diphtheriae can deliver highly nuanced data in order to inform targeted public health actions and policy for predicting the future impact of this highly successful pathogen.

microbiology↗