Biology subjects

Duggan, S.

Publications and source records attributed to Duggan, S..

6 recordsLinked to original sources

bioRxiv2026

Antarctic marine microplastics reveals environmental persistence and rapid evolution of Candida auris

Candida (Candidozyma) auris is a critical priority fungal pathogen that emerged two decades ago near simultaneously on multiple continents. Since emergence, C. auris resistance to all four classes of antifungal drugs has been described, including pan-drug resistant isolates, sometimes evolving within patients. Here, we confirm the first isolation of C. auris from Antarctica and show cold-adapted phenotypes and an affinity for binding to nylon. We also provide evidence to suggest mutator phenotypes contribute to the rapid evolution of C. auris and are responsible for the emergence of multiple, distinct genetic clades worldwide. Isolates in clades I, III and IV with a mutator phenotype displayed elevated mutation rates compared to non-auris Candida species. This phenotype had a complex genetic basis and was associated with drug resistance mutations. We postulate that the mutator phenotype has a significant effect on evolutionary potential and is responsible for the emergence and rapid spread of drug-resistance C. auris and novel genetic clades.

microbiology↗

bioRxiv2025

Copper Driven Mutualism of Candida albicans and Staphylococcus aureus Interkingdom Biofilms

Although fungi and bacteria commonly coexist within polymicrobial communities, the molecular mechanisms underlying their interactions are still not well understood. Here, we show that the fungus Candida albicans forms biofilms with the bacterium Staphylococcus aureus along a nutritional axis of mutualism and propose that "a copper economy" shapes fungal-bacterial biofilm interactions. Using in vitro biofilms formed on plastic, we found that dual species biofilms are consistently larger than single-species counterparts, indicating a cooperative interaction. Dual species proteomic analysis revealed non-reciprocal copper handling: C. albicans increased copper uptake via transporter Ctr1, while S. aureus enhanced copper export via regulator CsoR and export chaperone CopZ. Dual species biofilms exhibited specific sensitivity to both copper depletion and supplementation, with corresponding reductions in biomass. We identified fungal copper import as the crucial element in mutualistic interactions between C. albicans and staphylococcal species. Moreover, fungal hyphae served as a critical scaffold for biofilm architecture, a role that was compromised under copper-replete conditions. Notably, copper nanoparticles disrupted these dual species biofilms, highlighting a potential therapeutic avenue. Furthermore, we extend the role of C. albicans copper import to mutualistic interactions with additional bacterial species. Our findings establish copper as a central mediator of C. albicans and S. aureus cooperation and suggest that a "copper economy" underpins mutualistic interactions in biofilms.

microbiology↗

bioRxiv2023

Lipoteichoic acid biosynthesis by Staphylococcus aureus is controlled by the MspA protein through competitive interference.

Staphylococcus aureus produces a plethora of virulence factors critical to its ability to establish an infection and cause disease. We have previously characterised a small membrane protein, MspA, which has pleiotropic affects on virulence and contributes to S. aureus pathogenicity in vivo. Here we report that mspA inactivation triggers overaccumulation of the essential cell wall component lipoteichoic acid (LTA) which, in turn, decreases autolytic activity and leads to increased cell size due to a delay in cell separation. We show that MspA directly interacts with the LTA synthesis enzymes UgtP, LtaA and LtaS, and competitively interferes with the association between LtaA and LtaS. While complementation of the mspA mutant with wild-type mspA reduces the amount of LTA, expression of a mutated version of MspA that does not interfere with the interactions between LtaA and LtaS does not. We suggest that MspA contributes to maintaining a physiological level of LTA in the cell wall by interacting with the LTA synthetic enzymes. In conclusion, this study uncovers the critical role of the MspA protein in regulating cell envelope biosynthesis and pathogenicity. IMPORTANCEThe S. aureus cell envelope, comprising of the cytoplasmic membrane, a thick peptidoglycan layer and the anionic polymers lipoteichoic acid and wall teichoic acids, is fundamental for bacterial growth and division, as well as being the main interface between the pathogen and the host. It has become increasingly apparent that the synthesis and turnover of cell envelope components also affect the virulence of S. aureus. In this study, we show that MspA, a novel effector of S. aureus virulence, contributes to the maintenance of normal levels of lipoteichoic acid in the cell wall, with implications on cell cycle and size. These findings further our understanding of the connections between envelope synthesis and pathogenicity and suggests MspA as a novel a target for therapeutic intervention.

microbiology↗

bioRxiv2022

Wall teichoic acids facilitate the release of toxins from the surface of Staphylococcus aureus.

A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm, through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures, however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilising a genome-wide association approach we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA is required for the release of several cytolytic toxins from the bacterial cells. We show this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to this process that requires in-depth investigation, while also demonstrating that clinical isolates can utilise WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities. ImportanceThe production and release of cytolytic toxins is a critical aspect to the pathogenicity of many bacterial pathogens. In this study we demonstrate a role for wall teichoic acids, molecules that are anchored to the peptidoglycan of the bacterial cell wall, in the release of toxins from S. aueus cells into the extracellular environment. Our findings suggest this effect is mediated by a gradient of electrostatic charge the presence of the negatively charged WTA molecules create across the cell envelope. This work brings an entirely new aspect to our understanding of the cytotoxicity of S. aureus and demonstrates a further means by which this major human pathogen can adapt its pathogenic capabilities.

microbiology↗

bioRxiv2021

The MpsB protein contributes to both the toxicity and immune evasion capacity of Staphylococcus aureus.

Understanding the role specific bacterial factors play in the development of severe disease in humans is critical if new approaches to tackle such infections are to be developed. In this study we focus on genes we have found to be associated with patient outcome following bacteraemia caused by the major human pathogen Staphylococcus aureus. By examining the contribution these genes make to the ability of the bacteria to survive exposure to the antibacterial factors found in serum, we identify three novel serum resistance associated genes, mdeA, mpsB and yycH. Detailed analysis of an MpsB mutant supports its previous association with the slow growing SCV phenotype of S. aureus, and we demonstrate that the effect this mutation has on membrane potential prevents the activation of the Agr quorum sensing system, and as a consequence the mutant bacteria do not produce cytolytic toxins. Given the importance of both toxin production and immune evasion to the ability of S. aureus to cause disease, we believe these findings explain the role of the mpsB gene as a mortality-associate locus during human disease.

microbiology↗

bioRxiv2019

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen, where the widespread emergence of antibiotic resistance is making infections more challenging to treat. Toxin induced tissue damage and resistance to the hosts immune system are well established as critical to its ability to cause disease. However, recent attempts to study S. aureus pathogenicity at a population level have revealed significant complexity and hierarchical levels of regulation. In an effort to better understand this we have identified and characterized a principle effector protein, MasA. The inactivation of this small highly-conserved membrane protein simultaneously disrupts toxin production and impairs S. aureus ability to resist several aspects of the innate immune system. These pleiotropic effects are mediated by both a change in the stability of the bacterial membrane and the dysregulation of iron homeostasis, which results in a significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and a sepsis model of infection. That proteins with such major effects on pathogenicity remain unidentified in a bacterium as well studied as S. aureus demonstrates how incomplete our understanding of their ability to cause disease is, an issue that needs to be addressed if effective control and treatment strategies are to be developed.

microbiology↗