Biology subjects

French, S.

Publications and source records attributed to French, S..

8 recordsLinked to original sources

bioRxiv2026

Honey bee (Apis mellifera) gut microbiome associations with viruses and pesticides across Canadian agroecosystems

The honey bee (Apis mellifera) gut microbiome plays a central role in host health, yet its variation across agricultural landscapes remains poorly resolved. This study investigates how major environmental stressors, particularly pesticide exposure and RNA virus loadings, shape the honey bee gut microbiome in a large-scale field study conducted across Canada, spanning diverse agroecosystems from British Columbia to Quebec. We identify consistent associations between specific bacterial taxa and major RNA viruses, including enrichment of Serratia marcescens with SBV and depletion of Bombella intestini with BQCV. Pesticide exposure is likewise linked to reproducible shifts in key microbial taxa. Together, these findings reveal that interacting stressors jointly shape the bee gut microbiome and enable prediction of microbiome responses in agroecosystems. HighlightsDistinct associations identified between gut bacteria and major bee RNA viruses (BQCV, SBV, LSV, IAPV) Pesticide exposure is linked to reproducible shifts in key microbial taxa Combined virus-pesticide effects form coordinated clusters that predict microbiome variation and specific bacterial responses Integrated modeling demonstrates that environmental stressors can jointly explain microbiome structure beyond crop effects Graphical abstractSchematic overview of potential links between pesticide exposure and RNA virus infection and their effects on the bee gut bacterial community. Solid arrows indicate associations supported by the present study, whereas dashed arrows indicate hypothesized or unresolved interactions. Associations between the presence of specific bee RNA viruses (left) or pesticide residues (right) and changes in the relative abundance of particular gut taxa (pink {uparrow}, increased; blue {downarrow}, decreased). The pesticide subtype is indicated by the icon in the cell (leaf - herbicide, hyphae - fungicide and insect - insecticide). Several bacterial taxa showed reproducible associations with specific viral or pesticide variables, including Bombella intestini, Serratia marcescens, Melissococcus plutonius, Paenibacillus alvei, Apibacter sp. wkB309, and Gilliamella sp. A7. Abbreviations: BQCV Black queen cell virus; LSV, Lake Sinai virus; SBV, Sacbrood virus; IAPV, Israeli acute paralysis virus. (p/n/b) indicate the sample matrix in which the pesticide was detected, namely pollen, nectar, and bee tissue, respectively. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/731697v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@cb92a4org.highwire.dtl.DTLVardef@1087045org.highwire.dtl.DTLVardef@102cabforg.highwire.dtl.DTLVardef@4ce2f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2026

Establishment of snake venom gland organoids from a novel family, Colubridae

Non-front-fanged snakes are abundant, diverse and represent approximately 70% of extant snakes. However, there is limited knowledge about most species and their venoms, in part due to the technical and welfare challenges associated with venom extraction, low venom yields, and the lack of cellular models available. Organoids represent an excellent opportunity to overcome these challenges. Here, we establish, for the first time, venom gland organoids from snakes of the Colubridae family and demonstrate the in vitro production of toxins.

bioengineering↗

bioRxiv2024

Micro-plaque assays: A high-throughput method to detect, isolate, and characterize bacteriophages

The gold standard for the isolation and characterization of bacteriophages (phages), the plaque assay, has remained almost unchanged for over 100 years. The need for improvements to its scalability has been driven home by successes with personalized phage therapy requiring large phage libraries and rapid sensitivity testing. Using a robotic pinning platform, we miniaturized plaque assays from bacterial lawns to micro-colonies from 100 nl of inoculant, increasing throughput by >1000 fold without compromising sensitivity. A comparable manual workflow with one quarter the throughput maintained the same sensitivity. These micro-plaque assays can replace plaque assays as a new gold standard in phage biology. As proof of principle, we used our technique to isolate and de-replicate 21 unique Pseudomonas aeruginosa phages from a single environmental sample. We then demonstrated - using the same assay - that of 17 multi-drug resistant clinical P. aeruginosa strains, 15 were susceptible to infection by one or more of the 21 phages tested. Our method allows rapid isolation and de-replication of phages, as well as enabling screening of large phage libraries against bacterial isolates of interest.

microbiology↗

bioRxiv2022

Central metabolism is a key player in E. coli biofilm stimulation by sub-MIC antibiotics

Exposure of Escherichia coli to sub-inhibitory antibiotics stimulates biofilm formation through poorly characterized mechanisms. Using a high-throughput Congo Red binding assay to report on biofilm matrix production, we screened [~]4000 E. coli K12 deletion mutants for deficiencies in this biofilm stimulation response. Mutants lacking acnA, nuoE, or lpdA failed to respond to sub-MIC novobiocin, implicating central metabolism and aerobic respiration in biofilm stimulation. These genes are members of the ArcA/B regulon - controlled by a respiration-sensitive two-component system. Mutants of arcA and arcB had a pre-activated phenotype, where biofilm formation was already high relative to wild type in vehicle control conditions and failed to increase further with the addition of sub-MIC antibiotics. Supporting a role for respiratory stress, the biofilm stimulation response was inhibited when nitrate was provided as an alternative electron acceptor. Deletion of genes encoding the nitrate respiratory machinery abolished its effects, and nitrate respiration increased during growth with sub-MIC antibiotics. In probing the generalizability of biofilm stimulation, we found that the stimulation response to translation inhibitors was minimally affected by nitrate supplementation. Finally, using a metabolism-sensitive dye, we showed spatial co-localization of increased respiration with sub-MIC bactericidal antibiotics. By characterizing the biofilm stimulation response to sub-MIC antibiotics at a systems level, we identified multiple avenues for design of therapeutics that impair bacterial stress management.

microbiology↗

bioRxiv2022

Repeated birth injuries lead to pelvic floor muscle dysfunction and impairment in regeneration

ObjectivesChildbirth is a key risk factor for pelvic floor muscle (PFM) injury and dysfunction, and subsequent pelvic floor disorders (PFDs). Multiparity further exacerbates these risks. Using the pre-clinical rat model of simulated birth injury (SBI), we previously identified that an SBI leads to PFM atrophy and fibrosis. We hypothesized that multiple SBIs further overwhelm PFM regenerative capacity, leading to functionally relevant pathological alterations long-term. Study DesignRats underwent SBI and were allowed to recover for 8 weeks to undergo another SBI. Animals were sacrificed at acute, subacute, and long-term time points post-second injury (N=3-6/time point), and pubocaudalis (PCa) was harvested to assess ex vivo muscle function, histomorphological properties and gene expression. ResultsAcutely following the 1st SBI, PCa force was decreased relative to controls. At 4 weeks, PCa force was recovered and remained unchanged at 8 weeks. Similarly, lower PCa force was observed immediately after repeated SBI. In contrast to functional recovery after 1st SBI, PCa force remained lower at 4 weeks post-2nd SBI and continued to be decreased even after 12 weeks after repeated injury. Fiber size was smaller at the long-term time points after 2nd SBI compared to controls and single SBI groups. As opposed to the resolution of centralized nuclei at 8 weeks post-1st SBI, regenerating myofibers persisted even at 12 weeks post-2nd SBI. In contrast to the peak of collagen content at 4 weeks post-1st SBI, this parameter raised progressively over 12 weeks after repeated SBIs. Prolonged inflammatory response, impairment in muscle anabolism, and sustained expression of ECM remodeling genes were observed after repeated SBIs. ConclusionsRepeated birth injuries delay PFM regeneration and impair function in the pre-clinical rat model.

physiology↗

bioRxiv2021

Pro-regenerative Extracellular Matrix Hydrogel Prevents and Mitigates Pathological Alterations of Pelvic Muscles Following Birth Injury

Pelvic floor disorders, which include pelvic organ prolapse, and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Even though childbirth, specifically vaginal delivery, has been long recognized as the most important potentially modifiable risk factor for PFM injury, the precise mechanisms of PFM dysfunction following childbirth remain elusive. In this study we demonstrate that PFMs undergo atrophy and severe fibrosis in parous women with symptomatic pelvic organ prolapse compared to age-matched nulliparous cadaveric donors without history of pelvic floor disorders. These pathological alterations are recapitulated in the pre-clinical rat model of simulated birth injury. The transcriptional signature of PFMs post-injury demonstrates a sustained inflammatory response, impairment in muscle anabolism, and persistent expression of extracellular matrix (ECM) remodeling genes. Next, we evaluated the administration of acellular injectable skeletal muscle extracellular matrix hydrogel for the prevention and mitigation of these pathological alterations. Treatment of PFMs with the biomaterial either at the time of birth injury or 4 weeks post-injury reduced muscle atrophy and mitigated fibrotic degeneration. By evaluating gene expression, we demonstrate that these changes are mainly driven by the hydrogel-induced modulation of the immune response and intramuscular fibrosis, as well as enhancement of the endogenous myogenesis. This work furthers our understanding of PFM birth injury and demonstrates proof-of-concept for a new pragmatic pro-regenerative biomaterial approach for treating injured PFMs.

bioengineering↗

bioRxiv2018

The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection

Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host - a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C. auris also poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins in C. auris, with sequence as well as 3-D structural homologies to the major adhesin/invasin of C. albicans, Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognized C. auris in vitro, blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels of C. auris cross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethal C. auris disseminated infection, compared to the control alum-vaccinated mice. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, against C. auris candidemia. Identification of Als3-like adhesins in C. auris makes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against other Candida species and safety as well as efficacy in clinical trials. Considering that C. auris can be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance.\n\nAuthor SummaryCandida auris has emerged as a major health concern to hospitalized patients and nursing home subjects. C. auris strains display multidrug resistance to current antifungal therapy and cause lethal infections. We have determined that C. auris harbors homologs of C. albicans Als cell surface proteins. The C. albicans NDV-3A vaccine, harboring the N-terminus of Als3p formulated with alum, generates cross-reactive antibodies against C. auris clinical isolates and protects neutropenic mice from hematogenously disseminated C. auris infection. Importantly, the NDV-3A vaccine displays an additive protective effect in neutropenic mice when combined with micafungin. Due to its proven safety and efficacy in humans against C. albicans infection, our studies support the expedited testing of the NDV-3A vaccine against C. auris in future clinical trials.

microbiology↗

bioRxiv2018

A macrophage-based screen identifies antibacterial compounds selective for intracellular Salmonella Typhimurium

Salmonella Typhimurium (S. Tm) evades the innate immune response by residing within host phagocytes. To identify inhibitors of intracellular S. Tm growth, we performed parallel chemical screens against S. Tm growing in macrophage-mimicking media and within macrophages. These screens identified novel antibacterials, and revealed that antibiotics with limited Gram-negative coverage are active against intracellular S. Tm. Screening of a S. Tm deletion library in the presence of one compound, metergoline, revealed that outer membrane perturbation enhanced activity in vitro. Combined with our observation of atypical cell surface characteristics of intracellular S. Tm, our work indicates that the bacterial outer membrane is permeabilized within macrophages. We show that metergoline targets the bacterial cytoplasmic membrane, and prolongs animal survival during a systemic S. Tm infection. This work highlights the predictive nature of intracellular screens for in vivo efficacy, and uncovers new aspects of bacterial physiology of intracellular S. Tm.

microbiology↗