Biology subjects

Hill-Yardin, E. L.

Publications and source records attributed to Hill-Yardin, E. L..

5 recordsLinked to original sources

bioRxiv2025

Efficacy of a bacteriophage cocktail targeting pathogenic bacteria associated with gastrointestinal dysfunction

The use of bacteriophage viruses that infect and kill bacteria is increasingly explored as an alternative to antibiotics for treatment of infections caused by opportunistic pathogens. Examples of opportunistic pathogens that disrupt the intestinal barrier and contribute to microbial imbalance in the gastrointestinal tract include Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens. This study evaluated the in vitro effectiveness of a bacteriophage cocktail composed of three host-specific phages: Lilla1 targeting Klebsiella pneumoniae, PAE1 targeting Pseudomonas aeruginosa and Smarc1 targeting Serratia marcescens. Bacterial growth was monitored by measuring optical density at 600 nm, and phage replication was quantified by plaque-forming unit assays. Each phage exhibited strong host specificity and produced significant reduction of growth of the corresponding bacterium while increasing in concentration during incubation. When applied as a cocktail, these three phages produced stronger and more sustained suppression of bacterial growth than single-phage treatments, both in individual cultures and in mixed cultures containing all three pathogens. In mixed cultures, continuous inhibition of bacterial growth persisted throughout a 24-hour incubation, and concentrations of Lilla1, PAE1 and Smarc1 increased significantly, indicating active replication and enhanced efficacy in combination. In single bacterial growth assays, bacterial populations that were initially suppressed showed regrowth after extended incubation. Regrowth manifested as a renewed increase in optical density several hours after initial decline and is consistent with selection of phage-resistant subpopulations, potentially arising from modification of surface receptors, phase variation or activation of adaptive defence systems. The observed biphasic response highlights the need for measures to limit microbial resistance to phage treatment, including expanded phage cocktails, adjusted dosing strategies and combined phage-antibiotic regimens. The results demonstrate that a three-phage cocktail can simultaneously inhibit multiple bacterial pathogens associated with gastrointestinal dysfunction and provide a basis for further in vivo evaluation and therapeutic development.

microbiology↗

bioRxiv2025

Bioengineered visible polymeric mesh to enhance urogynaecological health

Pelvic floor disorders, including pelvic organ prolapse and stress urinary incontinence, are prevalent health concerns, affecting approximately 50% of females over their lifetime, with about 75% of women over 65 years of age being impacted. Traditional surgical interventions, such as transvaginal mesh implants, have led to numerous complications, resulting in their prohibition in several countries. This study introduces an innovative composite mesh designed to mitigate these issues by combining polymethylmethacrylate and thermoplastic polyurethane, further enhanced with iodine-doped carbon nanoparticles to enable visibility via medical imaging. The mesh is coated with 2-methacryloyloxyethyl phosphorylcholine polymer to prevent protein adsorption and promote tissue regeneration. In vitro studies showed high cell viability and low protein adsorption, indicating excellent biocompatibility. Implantation of mesh (with or without iodine) in mice revealed no adverse effects on overall animal health. Mouse spleen weight (an indicator of inflammation) was similar between groups; however, levels of some cytokines (i.e., IL-10, IL-17A and GM-CSF) were elevated following implantation of iodinated mesh in mice suggesting that further refinement of the composite mesh is required. Analysis of the fecal microbiome, which is correlated with physiological states, showed that sham and iodinated mesh implant groups maintained consistent microbial profiles with stable diversity (richness and evenness) measures over time. In contrast, the non-iodinated mesh group exhibited decreased species richness post mesh implantation, likely due to a distinct starting microbiome composition prior to implantation. This research is envisaged to contribute to a safer and more effective solution for treating pelvic floor disorders, providing non-invasive post-implantation monitoring and enhanced mechanical compatibility of surgical mesh with native tissue. Our findings demonstrate that this composite mesh possesses mechanical properties that closely mimic human tissue, ensuring biocompatibility, strength, and flexibility without stimulating significant inflammatory or foreign body responses.

bioengineering↗

bioRxiv2022

The autism-associated Neuroligin-3 R451C mutation alters mucus density and the spatial distribution of bacteria in the mouse gastrointestinal tract

The intestinal mucus layer protects the host from invading pathogens and is essential for maintaining a healthy mucosal microbial community. Alterations in the mucus layer and composition of mucus-residing microbiota in people diagnosed with Autism Spectrum Disorder (ASD; autism) may contribute to dysbiosis and gastrointestinal (GI) dysfunction. Although microbial dysbiosis based on sequencing data is frequently reported in autism, spatial profiling of microbes adjacent to the mucosa is needed to identify changes in bacterial subtypes in close contact with host tissues. Here, we analysed the spatial distribution of the MUC-2 protein using immunofluorescence as well as total bacteria, Bacteroidetes, Firmicutes phyla and Akkermansia muciniphila (A. muciniphila) using fluorescent in situ hybridization in mice expressing the autism-associated R451C mutation in the Neuroligin-3 (Nlgn3) gene. We show that the Nlgn3 R451C mutation increases mucus density adjacent to the distal ileal epithelium in mice. The relative density of total bacteria, Firmicutes and A. muciniphila was increased whereas the density of Bacteroidetes was decreased closer to the epithelium in Nlgn3R451C mice. In summary, this study suggests that increased mucus density could contribute to mucosal microbial dysbiosis in ASD.

neuroscience↗

bioRxiv2022

Quantitative analysis of neuroligin-3 expression in the enteric nervous system of the Neuroligin-3R451C mouse model of autism

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but its cellular expression in the GI tract remains to be characterised. Localisation of NLGN3 protein is challenging in intestinal tissue due to the lack of target-specific antibodies. Here, we combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for markers of all enteric neurons, cholinergic submucosal neurons, non-cholinergic submucosal neurons, nitregic and calretinin-containing myenteric neurons as well as glial cells. We also developed a quantitative 3-dimensional image analysis method to measure Nlgn3 mRNA cellular expression levels in enteric neurons and glia. We show that Nlgn3 mRNA is expressed in most submucosal and myenteric neurons as well as in enteric glia. The R451C mutation reduces Nlgn3 mRNA expression levels in cholinergic, nitrergic and calretinin enteric neuronal subpopulations but does not affect Nlgn3 mRNA expression in VIPergic submucosal neurons. In summary, we show that the autism-associated R451C mutation in Nlgn3 reduces Nlgn3 mRNA expression in the mouse ENS. These findings could shed light on the pathophysiology of GI dysfunction in ASD.

neuroscience↗

bioRxiv2022

Hyperimmune bovine colostrum containing lipopolysaccharide antibodies (Imm124-E) has a non-detrimental effect on gut microbial communities in unchallenged mice.

1Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea in travelers, military personnel and children in developing countries. Infection has the potential to cause long-term gastrointestinal dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on gastrointestinal commensals in healthy individuals is unclear. Whether administration of a prophylactic preventative treatment for ETEC-induced diarrhea causes specific shifts in gut microbial populations in controlled environments is also unknown. Here we studied the effects of a hyperimmune bovine colostrum (IMM-124E) used in the manufacture of Travelan(R) (AUST L 106709) on gastrointestinal bacteria in healthy C57BL/6 mice. Using next generation sequencing, we aimed to test the onset and magnitude of potential changes to the mouse gut microbiome in response to the anti-diarrheagenic hyperimmune bovine colostrum product, rich in immunoglobulins against select ETEC strains (Travelan(R), Immuron Ltd). We engineered changes in mouse fecal and cecal bacterial communities by delivering lipopolysaccharide (LPS) antibodies derived from bovine colostrum via dietary supplementation. Holstein Friesian and Jersey cows between 28- and 35-weeks gestation stimulated by subcutaneous delivery of three important pathogenic and antigenic determinants; LPS, flagella, and colonization factor antigen (CFA), produced a hyperimmune colostrum (IMM-124E) with demonstrated beneficial effects on health via modulation of metabolic pathways and immune function. We show that in mice administered colostrum containing LPS antibodies there was an increased abundance of potentially gut-beneficial bacteria, such as Akkermansia and Desulfovibrio, without disrupting the underlying ecology of the gastrointestinal tract. Compared to controls, there was no difference in overall weight gain, body or cecal weights or small intestine length following LPS antibody colostrum supplementation. Overall, dietary supplementation with colostrum containing LPS antibodies produced subtle alterations in gut bacterial composition of mice. Primarily, Travelan(R) LPS antibody treatment decreased the ratio of Firmicutes/Bacteroidetes in gut microbial populations in unchallenged healthy mice. Further studies are required to examine the effect of Travelan(R) LPS antibody treatment to engineer the microbiome in a diseased state and during recovery.

microbiology↗