Biology subjects

Forde, T. L.

Publications and source records attributed to Forde, T. L..

7 recordsLinked to original sources

bioRxiv2026

Home is where the host is: Evolutionary history of geographic spread, host switching, and adaptive genomic signatures in two generalist Group B Streptococcus clonal groups

Group B Streptococcus (GBS) is a pathogen of global relevance in neonatal and maternal disease as well as bovine mastitis. Two closely related clonal groups, denoted 103 and 314 (CG103/314) have been detected in humans and cattle on multiple continents in recent decades but are poorly characterised compared to other host-generalist clades. We examined their potential origins, host-switching events and presence of a suite of genetic markers for antimicrobial resistance, virulence and host association using a newly assembled dataset of 248 CG103/314 genomes from humans, cattle, and food originating from five continents. We detected multiple host switches between humans and cattle, and significant regional differences in AMR gene distribution, possibly reflecting local differences in antimicrobial use across countries and hosts and indicating a capacity for regional adaptation to selective pressures. Across the evolutionary history of CG103/314 from both host species, the prevalence of the Lac.2 operon, a genetic marker associated with bovine host adaptation, was high, whereas the prevalence of the scpB-lmb gene pair, a genetic marker of human host adaptation in other GBS clonal groups, was very low. All isolates with scpB-lmb were associated with human disease rather than carriage. Our dataset displayed biases typical of research into multi-host pathogens, when sampling is often focused on a specific host species or setting. Consistent, balanced, contemporaneous and sympatric sampling efforts across host species and sources are needed for a full understanding of the distribution and emergence of CG103/314 and similar multi-host pathogens impacting food safety and public health. Impact statementThis study provides a comprehensive, global genomic overview of generalist clonal groups 103/314 of the human and animal pathogen Group B Streptococcus (GBS). By analysing host switching, antimicrobial resistance and virulence-associated markers, we show that these clonal groups display adaptation patterns shaped by region- and host-specific selective pressures. Our findings include potential expansion of the host range from humans and cattle into porcupines and pigs, and provides detailed discussion around anthropocentric sampling bias, highlighting the importance of balanced, multi-host sampling of generalist GBS lineages and One Health pathogens in general. This work reinforces the need for coordinated One Health surveillance to monitor emerging sub-lineages with relevance for food safety, human and animal health.

evolutionary biology↗

bioRxiv2025

Investigating Bacillus anthracis genomic diversity and trait-specific lineages in an endemic area in northern Tanzania through a combination of traditional and culture-free sequencing approaches

Anthrax, caused by Bacillus anthracis (BA), is a prominent neglected zoonosis with major impacts on human, livestock, and wildlife health. Despite this, limited genomic investigation at the One Health interface constrains current understanding of BA transmission and of the ecological and host factors shaping its diversity and population structure. This includes the possibility of host-specific BA lineages, given that anthrax outbreaks often disproportionally affect individual species. This study characterises the genomic diversity of BA in an endemic area, the Ngorongoro Conservation Area (NCA), in northern Tanzania. We analysed 213 BA genomes from livestock, wildlife and humans from cultured isolates combined with a culture-free targeted capture (TC) approach. NCA sequences formed a distinct genetic cluster compared with those from surrounding areas, and we observed surprisingly high levels of strain diversity within apparent epidemiological clusters, as well as within single animals, though strain diversity was lowest at the within host scale. We found limited evidence for seasonal clustering of cases as well as for BA lineages clustering by host species. This indicates that disproportional impacts on certain species during outbreaks are more likely driven by host ecology factors or, hypothetically, by accessory parts of the bacterial genome not represented in our data. TC-derived data significantly expanded the range of host species and geographic locations for genomic analysis, demonstrating the value of this approach. Although TC data may contain artefactual variation, shared SNP profiles between isolate- and TC-derived genomes gave confidence in its use for genotyping. Our analysis demonstrates unexpectedly high BA strain diversity and limited population structure in this endemic area across a range of spatial scales, including within-host. It further highlights the need for high density sampling and adaptable sequencing strategies to generate adequate BA genomic datasets that can enable informative molecular epidemiological studies of anthrax at the One Health interface. Author SummaryAnthrax continues to threaten the health of people, livestock, and wildlife in many parts of the world, yet we still know surprisingly little about how this disease spreads in nature. One major gap is understanding why some species are affected more strongly during outbreaks, despite assumed equal susceptibility. To investigate this, we studied the genomic diversity of the anthrax-causing bacterium Bacillus anthracis in a large conservation area in northern Tanzania. We combined two ways of generating genetic data: traditional laboratory culture and a culture-free method that allowed us to recover bacterial DNA from a wider range of samples. By analysing a uniquely large and species-diverse dataset of over 200 bacterial genomes from people, livestock and wildlife, we found that bacteria from the study area formed a clearly defined group compared to those from surrounding regions. We also discovered unexpectedly high diversity of strains, not only across the landscape but even within single animals. Despite this diversity, we saw little evidence that certain bacterial lineages are tied to specific host species. Our results suggest that the behaviour and ecology of different animals, rather than host-adapted lineages of the bacterium, likely explain why some species are more affected than others.

genomics↗

bioRxiv2023

Three Accessory Gene Clusters Drive Host-Adaptation in Group B Streptococcus

Streptococcus agalactiae (Group B Streptococcus, GBS) is a major pathogen of humans and animals, posing a threat to human health as well as food security. Here, we investigate the role of genomic mechanisms, including homologous recombination and horizontal gene transfer, in shaping the population structure of GBS and its adaptation to three major host groups (humans, cattle, fishes). We demonstrate that the GBS population comprises host-specialist, host-adapted lineages as well as host generalists, and that these categories differ in their level or recombination. Although the accessory genome at large varies by lineage rather than host, genome wide association studies show that host association is driven by three accessory genome clusters, regardless of lineage or breadth of the host spectrum. These genomic clusters (scpB in human GBS, lactose operon in bovine GBS, Locus 3 in fish GBS) are known (scpB, Lac.2) or shown here (Locus 3) to be functionally relevant and are shared with other streptococcal species occupying the same host niche. These findings demonstrate the importance of considering the role of non-human host species in the evolution of GBS, including high risk clones that may lead to interspecies transmission and affect efficacy of future GBS vaccines.

genomics↗

bioRxiv2022

Genomic characterisation of a novel species of Erysipelothrix associated with mortalities among endangered seabirds

Infectious diseases threaten endangered species, particularly in small isolated populations. Seabird populations on the remote Amsterdam Island in the Indian Ocean have been in decline for the past three decades, with avian cholera caused by Pasteurella multocida proposed as the primary driver. However, Erysipelothrix spp. has also been sporadically detected from albatrosses on Amsterdam Island and may be contributing to some of the observed mortality. In this study, we genomically characterised 16 Erysipelothrix spp. isolates obtained from three Indian yellow-nosed albatross chick carcasses in 2019. Two isolates were sequenced using both Illumina short-read and MinION long-read approaches, which - following hybrid assembly - resulted in closed circular genomes. Mapping of Illumina reads from the remaining isolates to one of these new reference genomes revealed that all 16 isolates were closely related, with a maximum of 13 nucleotide differences distinguishing any pair of isolates. The nucleotide diversity of isolates obtained from the same or different carcasses was similar, suggesting all three chicks were likely infected from a common source. These genomes were compared with a global collection of genomes from E. rhusiopathiae and other species from the same genus. The isolates from albatrosses were phylogenetically distinct, sharing a most recent common ancestor with E. rhusiopathiae. Based on phylogenomic analysis and standard thresholds for average nucleotide identity and digital DNA-DNA hybridisation, these isolates represent a novel Erysipelothrix species, for which we propose the name Erysipelothrix amsterdamensis sp. nov. The type strain is E. amsterdamensis A18Y020dT. The implications of this bacterium for albatross conservation will require further study.

genomics↗

bioRxiv2022

Target-enrichment sequencing yields valuable genomic data for difficult-to-culture bacteria of public health importance

Genomic data contribute invaluable information to the epidemiological investigation of pathogens of public health importance. However, whole genome sequencing (WGS) of bacteria typically relies on culture, which represents a major hurdle for generating such data for a wide range of species for which culture is challenging. In this study, we assessed the use of culture-free target-enrichment sequencing as a method for generating genomic data for two bacterial species: 1) Bacillus anthracis, which causes anthrax in both people and animals and whose culture requires high level containment facilities; and 2) Mycoplasma amphoriforme, a fastidious emerging human respiratory pathogen. We obtained high quality genomic data for both species directly from clinical samples, with sufficient coverage (>15X) for confident variant calling over at least 80% of the baited genomes for over two thirds of the samples tested. Higher qPCR cycle threshold (Ct) values (indicative of lower pathogen concentrations in the samples), pooling libraries prior to capture, and lower captured library concentration were all statistically associated with lower capture efficiency. The Ct value had the highest predictive value, explaining 52% of the variation in capture efficiency. Samples with Ct values [≤] 30 were over 6 times more likely to achieve the threshold coverage than those with a Ct > 30. We conclude that target-enrichment sequencing provides a valuable alternative to standard WGS following bacterial culture and creates opportunities for an improved understanding of the epidemiology and evolution of many clinically important pathogens for which culture is challenging. Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Scripts used in this study can be accessed on GitHub at https://github.com/tristanpwdennis/bactocap. All sequence data generated during this study have been deposited in the European Nucleotide Archive (ENA) Sequence Read Archive (SRA) under project accession numbers PRJEB46822 (B. anthracis) and PRJEB50216 (M. amphoriforme). Accession numbers for individual samples, along with metadata, laboratory parameters and sequence quality metrics, are available at the University of Glasgows data repository, Enlighten, at http://dx.doi.org/10.5525/gla.researchdata.1249.

molecular biology↗

bioRxiv2021

Population genomics of Bacillus anthracis from an anthrax hyperendemic area reveals transmission processes across spatial scales and unexpected within-host diversity

Genomic sequencing has revolutionized our understanding of bacterial disease epidemiology, but remains underutilized for zoonotic pathogens in remote endemic settings. Anthrax, caused by the spore-forming bacterium Bacillus anthracis, remains a threat to human and animal health and rural livelihoods in low- and middle-income countries. While the global genomic diversity of B. anthracis has been well-characterized, there is limited information on how its populations are genetically structured at the scale at which transmission occurs, critical for understanding the pathogens evolution and transmission dynamics. Using a uniquely rich dataset, we quantified genome-wide single nucleotide polymorphisms (SNPs) among 73 B. anthracis isolates derived from 33 livestock carcasses sampled over one year throughout the Ngorongoro Conservation Area, Tanzania, an area hyperendemic for anthrax. Genome-wide SNPs distinguished 22 unique B. anthracis genotypes within the study area. However, phylogeographic structure was lacking, as identical SNP profiles were found throughout the study area, likely the result of the long and variable periods of spore dormancy and long-distance livestock movements. Significantly, divergent genotypes were obtained from spatio-temporally linked cases and even individual carcasses. The high number of SNPs distinguishing isolates from the same host is unlikely to have arisen during infection, as supported by our simulation models. This points to an unexpectedly wide transmission bottleneck for B. anthracis, with an inoculum comprising multiple variants being the norm. Our work highlights that inferring transmission patterns of B. anthracis from genomic data will require analytical approaches that account for extended and variable environmental persistence as well as co-infection. ImportancePathogens transmitted between animals and people affect the health and livelihoods of farmers, particularly in developing countries dependent on livestock. Understanding over what distances these pathogens are transmitted and how they evolve is important to inform control strategies towards reducing disease impacts. Information on the circulation of Bacillus anthracis, which causes the often-lethal disease anthrax, is lacking for settings where the disease is commonplace. Consequently, we examined its genetic variability in an area in Tanzania where anthrax is widespread. We found no clear link between how closely cases were sampled and their genetic similarity. We suspect this lack of congruence is primarily driven by large-scale livestock movements, which control efforts should take into consideration. Another significant finding was the co-occurrence of multiple B. anthracis types within individual hosts, suggesting animals are commonly infected with a mixture of variants. This needs to be accounted for when investigating possible connections between cases.

genomics↗

bioRxiv2021

The fall and rise of group B Streptococcus in dairy cattle: reintroduction due to human-to-cattle host jumps?

Group B Streptococcus (GBS; Streptococcus agalactiae) is a major neonatal and opportunistic bacterial pathogen of humans and an important cause of mastitis in dairy cattle with significant impacts on food security. Following the introduction of mastitis control programs in the 1950s, GBS was nearly eradicated from the dairy industry in northern Europe, followed by re-emergence in the 21st century. Here, we sought to explain this re-emergence based on short and long read sequencing of historical (1953-1978; n = 44) and contemporary (1997-2012; n = 76) bovine GBS isolates. Our data show that a globally distributed bovine-associated lineage of GBS was commonly detected among historical isolates but never among contemporary isolates. By contrast, tetracycline resistance, which is present in all major GBS clones adapted to humans, was commonly and uniquely detected in contemporary bovine isolates. These observations provide evidence for strain replacement and suggest a human origin of newly emerged strains. Three novel GBS plasmids were identified, including two showing >98% homology with plasmids from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis, which co-exist with GBS in the human oropharynx. Our findings support introduction of GBS into the dairy population due to human to-cattle jumps on multiple occasions and demonstrate that reverse zoonotic transmission can erase successes of animal disease control campaigns. IMPACT STATEMENTPathogens can jump between humans and animals. Animal domestication and intensification of livestock production systems have caused multiple human to animal spill-over events, sometimes with significant impact on animal health and food production. The most common production-limiting disease of dairy cattle is mastitis, inflammation of the mammary gland, which can be caused by group B Streptococcus, a common commensal and pathogen of humans. Using genomic data from historical and recent isolates, we show that re-emergence of this pathogen in the dairy industry in northern Europe is due to strains with genomic signatures of human host-adaptation, including antimicrobial resistance genes and plasmids. This shows how elimination of animal diseases may be hampered by humans serving as a reservoir of multi-host pathogens, and reverse zoonotic transmission. REPOSITORIESReads for all isolates sequenced in this study have been submitted to the ENA Sequence Read Archive (SRA). SRA accession numbers are included in Table S1, supplementary material, available in the online version of this article.

genomics↗