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Journal articleBernard A, Ledesma-Amaro R, Rossignol T, et al., 2026,
Synthetic communities of Yarrowia lipolytica for efficient betanin bioproduction through metabolic partitioning
, Bioresource Technology, Vol: 461, ISSN: 0960-8524In bioproduction, synthetic microbial consortia have the potential to outcompete single-strain systems by distributing metabolic burden and partitioning tasks more effectively. Obligatory cross-feeding of essential metabolites, or syntrophy, is a promising strategy to stabilize consortium composition and prevent population drift. In this study, we screened 56 co-auxotrophic pairs capable of establishing syntrophy in the unconventional yeast Yarrowia lipolytica. Further characterization of these consortia revealed diverse growth dynamics and population distributions across various inoculation ratios. A selection of syntrophic consortia was evaluated for the production of the natural value-added pigment, betanin, as a proof-of-concept. By redistributing the metabolic load across different co-culture designs, we achieved higher betanin titers (136.2 mg/L) in syntrophic co-cultures compared to monoculture by 1.5-fold in microbioreactor conditions. This study provides a platform of Y. lipolytica syntrophic consortia to produce metabolically demanding compounds more efficiently.
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Journal articleAzbekyan G, Shirvanyan A, Guaragnella N, et al., 2026,
Oxygen-dependent regulation of ion fluxes and intracellular pH in Saccharomyces cerevisiae exposed to acetic acid
, Archives of Biochemistry and Biophysics, Vol: 786, ISSN: 0003-9861The study of acetic acid (AA) stress in yeast is crucial for understanding the mechanisms of acid stress tolerance and enhancing production efficiency. Although AA toxicity has been extensively studied, the mechanism by which oxygen availability modulates ion flux balance and intracellular proton handling under AA stress remains poorly understood. Here, we investigated the combined effects of AA concentration, acidic pH, and oxygen availability on plasma membrane Na+, K+, and H+ fluxes, intracellular pH, and growth in two Saccharomyces cerevisiae strains with distinct AA tolerance. We show that AA toxicity is strongly concentration-, strain-, and oxygen-dependent. AA exposure increased DCCD-sensitive proton (JH+) and sodium (JNa+) fluxes while progressively impairing potassium uptake (JK+), resulting in nonlinear, strain-specific shifts in Na+/H+ and K+/H+ exchange ratios and a substantial increase in ion exchange imbalance. These effects were amplified under oxygen-limited conditions and correlated with reduced growth and metabolic activity. Moderate AA stress was accompanied by increased intracellular ATP, particularly in ATCC 9804 under oxygen limitation, whereas severe AA stress caused ATP depletion, most strongly in ATCC 13007. Notably, the more tolerant strain maintained lower intracellular proton accumulation and more efficient ion flux coordination, particularly during aerobic growth. Together, our findings demonstrate that oxygen availability fundamentally reshapes ion flux balance and intracellular pH homeostasis during AA stress. These insights have direct implications for strain selection and process optimization in industrial fermentations exposed to weak organic acid inhibition.
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Journal articleGeorgakilas AG, Vasilopoulos SN, Bigiş EZ, et al., 2026,
Conserved host-exclusive oligonucleotide motifs enriched in pathogenic genes of human oncogenic viruses.
, Virology, Vol: 624Comparative viral genomics can reveal sequence-level constraints influencing virus-host interactions. Relative minimal absent words (rMAWs) are short oligonucleotide motifs present in viral genomes but completely absent from the host, potentially reflecting selective pressures related to host adaptation and immune evasion. Using the EAGLE algorithm and the GRCh38 human reference genome, we systematically screened for prevalent rMAWs (prMAWs) across six major human oncogenic viruses: Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), human T-cell leukemia virus type 1 (HTLV-1), and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). highly conserved 11- and 12-bp prMAWs were identified in EBV, HBV, HTLV-1, and HHV-8/KSHV, with sequence prevalences ranging from 91.5% to 97.9%. Conversely, no short prMAWs were detected in HCV or HPV, likely reflecting differences in genome architecture, mutation rates, and long-term host adaptation to the human host. Importantly, the identified host-exclusive motifs exhibited non-random genomic distribution and were preferentially embedded within viral genes central to replication, persistence, immune modulation, and oncogenesis, including EBNA-1 (EBV), HBx (HBV), Tax-associated regions (HTLV-1), and lytic replication genes of HHV-8/KSHV. Notably, all detected prMAWs were enriched in GC nucleotides and exhibited marked CpG over-representation, suggesting sequence constraints associated with epigenetic regulation and viral persistence. Collectively, these highly conserved, host-exclusive signatures offer promising, candidates for sequence-directed approaches in the diagnosis, monitoring, and investigation of virus-associated cancers.
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Journal articleGupta AK, Teasell EM, Wang T, et al., 2026,
Environmental Terbinafine Contamination and Dermatophyte Resistance: A One Health Hypothesis in Need of Ecological Validation.
, Mycopathologia, Vol: 191Terbinafine resistance in dermatophytes is an increasing global concern, driven in part by the intercontinental spread of Trichophyton indotineae. The current epidemic of dermatophyte resistance is primarily attributed to clinical and community factors, including inappropriate antifungal use and fixed-dose corticosteroid-antifungal combinations. However, environmental antifungal contamination has emerged as a potential but largely unexplored contributor to resistance selection, as has been proposed for azole resistance in other fungal pathogens. Here, we examine whether environmental terbinafine contamination represents an overlooked One Health selection pressure or, alternatively, an exposure signal whose relevance to dermatophyte resistance remains ecologically constrained. Terbinafine is highly lipophilic, partitions into organic matter, and has been detected in wastewater, sludge, biosolids, surface water, groundwater, and sediment. Reported concentrations vary markedly by region and sample type, and in some cases exceed proposed resistance-selection thresholds. However, most clinically important dermatophytes, particularly anthropophilic Trichophyton lineages, are host-associated keratinophilic fungi rather than free-living environmental saprobes. Therefore, environmental terbinafine is unlikely to drive resistance unless viable dermatophyte propagules, keratinous substrates, and biologically active drug residues co-occur in the same ecological niche. Current evidence is insufficient to determine whether environmental terbinafine contamination contributes meaningfully to dermatophyte resistance selection. While infected wildlife and geophilic dermatophytes may serve as useful sentinel systems, they do not yet establish a causal environmental pathway for the emergence or spread of resistant T. indotineae. In order to address these knowledge gaps, we propose that future One Health surveillance should integrate terbinafine quantification with dermat
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Journal articleAlferes de Lima Headley D, Richardson H, Hennayake C, et al., 2026,
Sputum and oral microbiota profiles are associated with long COVID severity and phenotype post-hospitalisation: a UK multicentre, prospective cohort study.
, Eur Respir JBACKGROUND: Acute COVID-19 alters the airway microbiota. Whether these changes persist post-COVID-19 and contribute to long COVID is unknown. We aimed to describe the microbiota by long COVID severity and subtype, and identify links with inflammation. METHODS: Adults were prospectively recruited to the longitudinal UK Post-hospitalisation COVID-19 study (PHOSP-COVID). Patients were grouped by previously described "severity clusters" (of ongoing health impairments) and symptom subgroups. Oral and sputum microbiota (at 6 months post-discharge) were characterised through 16S ribosomal RNA gene amplicon sequencing, and microbiota diversity was assessed. Co-occurrence network analysis identified keystone taxa. Associations between keystone taxa and plasma inflammatory proteins were assessed through Spearman's rank correlations. RESULTS: 771 participants had their microbiota assessed. Of participants with oral rinses and "severity cluster" assignment (mean age 57.5 years), 278 out of 722 (38.5%) were women. The "very severe" cluster, in which disease was predominantly pulmonary in nature, was associated with a distinct microbiota profile post-COVID-19. Reduced lung function was associated with a distinct oral microbiota profile. Persistent neurocognitive symptoms were associated with a distinct oral microbiota profile, while gastrointestinal symptoms were associated with a distinct sputum microbiota profile. Microbiota keystone taxa shifted to a higher prevalence of lactic acid bacteria associated with worse health outcomes. Lactic acid bacteria abundance was associated with elevated blood inflammatory proteins. CONCLUSION: Distinct oral and sputum microbiota profiles were associated with pulmonary function and with neurocognitive and gastrointestinal symptoms in long COVID. Shifts in keystone microbiota taxa linked with inflammation, based on worse health outcomes, suggest a potential role change for lactic acid bacteria, which may be a
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Journal articleSamir NM, Urayama S-I, Locke-Gotel J, et al., 2026,
Molecular characterization of a novel botourmiavirus infecting Leptosphaeria biglobosa.
, Arch Virol, Vol: 171The phytopathogenic fungus Leptosphaeria biglobosa is the host of diverse mycoviruses. Comprehensive analysis of next-generation sequencing (NGS) data obtained from purified double-stranded RNA (dsRNA) revealed the presence of three single-stranded RNA (ssRNA) molecules. These RNAs, designated ssRNA1, ssRNA2, and ssRNA3, are respectively 2,646, 683, and 575 bp in length. ssRNA1 contains a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRP) and represents the genome of a novel member of the family Botourmiaviridae, designated as "Leptosphaeria biglobosa botourmiavirus 3" (LbBoV-3). Conversely, ssRNA2 and ssRNA3 share identical 3'-termini but no other sequence similarity with ssRNA1, lack substantial ORFs, do not possess poly(A) tails, and are proposed to represent satellite-like RNAs associated with LbBoV-3. To our knowledge, LbBoV-3 is the second member of the genus Magoulivirus associated with two satellite RNAs, expanding the current understanding of mycoviral diversity associated with this economically important phytopathogenic fungus.
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Journal articleRuiz-Sanchis D, Ledesma-Amaro R, 2026,
Evolutionary engineering of synthetic microbial consortia in bioproduction
, Current Opinion in Biotechnology, Vol: 101, ISSN: 0958-1669Microbial consortia offer significant advantages over monocultures in biotechnological applications, including access to a broader metabolic repertoire, functional redundancy and the capacity for division of labour. Adaptive laboratory evolution (ALE) has similarly proven to be a powerful tool in metabolic engineering, uncovering solutions inaccessible through rational design alone. Despite their individual potential, the intersection of ALE and synthetic microbial consortia in bioproduction contexts remains underexplored. This review examines recent advances at this intersection, with a focus on bottom-up synthetic consortia and co-cultures.Artificial selection operates at organismal and supra-organismal levels in microbial communities, and this not only shapes their productive output, but it may also compromise the evolvability of costly production functions. This effect can be limited by engineering ecological interactions that stabilise community composition. ALE and synthetic consortia mutually expand each other's applicability through a variety of implementation logics. However, current approaches predominantly rely on growth-based selection, and we argue that implementing inter-community artificial selection strategies holds considerable untapped potential.
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Journal articlePugashetti JV, Jee AS, Yu AR, et al., 2026,
Mycophenolate and azathioprine in fibrotic interstitial lung disease
, American Journal of Respiratory and Critical Care Medicine, Vol: 212, Pages: 2493-2503, ISSN: 1073-449XRationaleImmunosuppression is routinely used for non–idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs), despite limited trial evidence and unclear impact on long-term outcomes.ObjectivesTo evaluate whether mycophenolate or azathioprine improves 3-year transplant-free survival and lung function trajectory in fibrotic ILD, including non-IPF idiopathic interstitial pneumonia (IIP), fibrotic hypersensitivity pneumonitis (fHP), and connective tissue disease (CTD)–associated ILD.MethodsWe employed a clone-censor-weighting framework to emulate a randomized controlled trial in this multicenter retrospective study. Each patient was cloned and assigned to immunosuppression initiation within 6 months of enrollment or no initiation strategies and censored when the assigned strategy deviated from observed treatment. Stabilized inverse probability treatment and censoring weights were used.MeasurementsThe primary endpoint was 3-year transplant-free survival assessed with weighted Cox models across treatment strategies. Weighted generalized estimating equations were used to model lung function trajectory.Main resultsAmong 2270 included patients, 18% (186/1022) with non-IPF IIP, 30% (162/544) with fHP, and 31% (221/704) with CTD-ILD were initiated on immunosuppression within 6 months. Immunosuppression was not associated with improved survival within any ILD subtype but was associated with worse survival in non-IPF IIP (hazard ratio [HR] = 1.38; 95% CI, 1.04-1.84) and fHP (HR = 1.62; 95% CI, 1.09-2.40). Immunosuppression was not associated with differential lung function trajectory within any ILD subtype.ConclusionsIn this study, immunosuppression initiation showed no evidence of benefit for 3-year transplant-free survival or lung function and was associated with higher mortality in select fibrotic ILD subtypes. Prospective randomized controlled trials are needed to inform patient care.
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Journal articleKhor YH, Luppi F, Adegunsoye A, et al., 2026,
Acute exacerbation in fibrotic interstitial lung disease: an international working group report.
, Am J Respir Crit Care Med, Vol: 212, Pages: 2358-2385Acute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and those with non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 International Working Group Report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AEs. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to diffuse alveolar damage in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.
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Journal articleDebabèche NB, Wagner M, Jiang Q, et al., 2026,
Cellulose sandwich composites with tube-reinforced foam cores.
, Carbohydr Polym, Vol: 389Lightweight porous cellulose materials, in particular pulp fibre foams, face challenges in achieving suitable mechanical properties while maintaining sustainability. Porous cellulose structures were developed by inserting pulp fibre pins or paper tubes into pre-perforated pulp fibre foams to form a sandwich structure with kraft liner paper deck sheets using a simple and scalable manufacturing process. The resulting porous cellulose composite structures, with densities ranging from 80 kg/m3 to 177 kg/m3, were mechanically characterised under compression, three-point bending, and double lap shear loading. We demonstrate that tube-reinforced configurations outperformed perforated pulp fibre foams in stiffness and strength, showing a significant improvement of 10,300% in compressive, 1500% in flexural, and 350% in shear modulus compared to perforated pulp fibre foams. We showed that the mechanical performance of pulp-based materials can be controlled by structural design rather than material modification, providing a viable strategy to overcome mechanical limitations of cellulose fibre foams.
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