Biology subjects

Gorzynski, J.

Publications and source records attributed to Gorzynski, J..

5 recordsLinked to original sources

bioRxiv2025

Immune-deficient bacteria serve as gateways to genetic exchange and microbial evolution

Horizontal gene transfer plays a key role in bacterial evolution, yet its efficiency under natural conditions, especially between genetically distinct strains, remains unclear. Using Staphylococcus aureus as a model, we found that gene transfer via various mechanisms is significantly restricted between strains from different clonal complexes (CCs), with the notable exception of lateral transduction, which occurs at high frequency. Interestingly, some strains exhibited a "promiscuous" ability to accept diverse mobile genetic elements. These strains were defective in the key immune defences of S. aureus, specifically the Type I restriction-modification systems that normally protect against foreign DNA. A broader analysis revealed that such immune-deficient mutants are widespread within S. aureus populations. Our study uncovered a trade-off that explains their persistence in nature: although these mutants are more susceptible to phage attack, they gain an evolutionary advantage by acquiring beneficial genes - such as those conferring antibiotic resistance - which enhance survival under selective pressure. These immune-deficient cells act as gateways for foreign DNA, which, once integrated and advantageous, can spread within the same CC. Our findings highlight an unexpected role for immune-deficient bacteria in facilitating the emergence of novel virulence factors and antibiotic resistance, emphasising their importance in shaping bacterial evolution.

microbiology↗

bioRxiv2024

Bacterial metabolic remodelling by convergent evolution in response to host niche-dependent nutrient availability

New pathogens often arise after host jump events between species. However, our understanding of how bacterial pathogens pivot to distinct nutrient availabilities in a new host niche is limited. Staphylococcus aureus is a multi-host pathogen responsible for a global burden of disease in humans and farmed animals. Multiple human-to-bovine host switching events led to the emergence of S. aureus as a leading cause of intramammary infection in dairy cattle. Here, we employed ex vivo milk infections to investigate how bovine S. aureus has adapted to the dairy niche revealing metabolic remodelling including upregulation of genes for lactose utilisation and branched-chain amino acid biosynthesis in response to nutrient availability. Notably, infection of milk by bovine S. aureus results in a milk clotting phenotype associated with enhanced bacterial growth that is dependent on the protease aureolysin. The same adaptive phenotype has evolved convergently in different bovine S. aureus lineages via mutations in distinct regulatory gene loci that promote enhanced aureolysin expression. Taken together, we have dissected a key adaptive trait for a bacterial pathogen after a host-switch event, involving metabolic remodelling in response to the availability of nutrients. These findings highlight the remarkable evolutionary plasticity of S. aureus underpinning its multi-host species tropism.

microbiology↗

bioRxiv2023

Leveraging whole genome sequencing to promote genetic diversity and population health in zoo-housed western lowland gorillas

The sustainability of zoo populations is dependent on maintaining genetic diversity and controlling heritable disease. Here, we explore the integration of whole genome sequencing data in the management of the international zoological population of western lowland gorillas, focusing on genetic diversity and heritable diseases. By comparing kinship values derived from classical pedigree mapping and whole genome sequencing, we demonstrate that genomic data provides a more sensitive measure of relatedness. Our analysis reveals a decrease in genetic diversity due to closed breeding, emphasizing the potential for genetic intervention to mitigate negative impact on population fitness. We identify contributing factors to the decreasing genetic diversity including breeding within a closed population, unknown kinship among potential mates, and disproportionate genetic contributions from individual founders. Additionally, we highlight idiopathic myocardial fibrosis (IMF), a common cardiovascular pathology observed in zoologically housed gorillas, and identify a novel genetic variant in the TNNI3K gene that appears to be associated with this condition. These findings underscore the importance of incorporating molecular data into ex-situ population management strategies, and advocate for the adoption of advanced genomic techniques to optimize the genetic health and diversity of zoologically housed western lowland gorillas.

zoology↗

bioRxiv2023

Local read haplotagging enables accurate long-read small variant calling

Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford nanopore technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy. However, using local haplotype information creates an overhead as variant calling needs to be performed multiple times which ultimately makes it difficult to extend to new data types and platforms as they get introduced. In this work, we have developed a local haplotype approximate method that enables state-of-the-art variant calling performance with multiple sequencing platforms including PacBio Revio system, ONT R10.4 simplex and duplex data. This addition of local haplotype approximation makes DeepVariant a universal variant calling solution for long-read sequencing platforms.

bioinformatics↗

bioRxiv2020

Population analysis of Legionella pneumophila reveals the basis of resistance to complement-mediated killing

Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires disease. L. pneumophila is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 900 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We found that although some clones are more commonly associated with clinical infections, the capacity for human disease is representative of the breadth of species diversity. To investigate the bacterial genetic basis for human disease potential, we carried out a genome-wide association study that identified a single gene (lag-1), to be most strongly associated with clinical isolates. Molecular evolutionary analysis showed that lag-1, which encodes an O-acetyltransferase responsible for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. Functional analysis revealed a correlation between the presence of a functional lag-1 gene and resistance to killing in human serum and bovine broncho-alveolar lavage. In addition, L. pneumophila strains that express lag-1 escaped complement-mediated phagocytosis by neutrophils. Importantly, we discovered that the expression of lag-1 confers the capacity to evade complement-mediated killing by inhibiting deposition of classical pathway molecules on the bacterial surface. In summary, our combined population and functional analyses identified L. pneumophila genetic traits linked to human disease and revealed the molecular basis for resistance to complement-mediated killing, a previously elusive trait of direct relevance to human disease pathogenicity. SignificanceLegionella pneumophila is an environmental bacterium associated with a severe pneumonia known as Legionnaires disease. A small number of L. pneumophila clones are responsible for a large proportion of human infections suggesting they have enhanced pathogenicity. Here, we employed a large-scale population analysis to investigate the evolution of human pathogenicity and identified a single gene (lag-1) that was more frequently found in clinical isolates. Functional analysis revealed that the lag-1-encoded O-acetyltransferase, involved in modification of lipopolysaccharide, conferred resistance to the classical pathway of complement in human serum. These findings solve a long-standing mystery in the field regarding L. pneumophila resistance to serum killing, revealing a novel mechanism by which L. pneumophila may avoid immune defences during infection.

microbiology↗