Publications

Journal article

Bernard A, Ledesma-Amaro R, Rossignol T, Park Y-Ket al., 2026,

Synthetic communities of Yarrowia lipolytica for efficient betanin bioproduction through metabolic partitioning

, Bioresource Technology, Vol: 461, ISSN: 0960-8524

In 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 article

Azbekyan G, Shirvanyan A, Guaragnella N, Ledesma-Amaro R, Trchounian Ket 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: 0003-9861

The 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.

Journal article

Georgakilas AG, Vasilopoulos SN, Bigiş EZ, Kotta-Loizou I, Pavlopoulou Aet al., 2026,

Conserved host-exclusive oligonucleotide motifs enriched in pathogenic genes of human oncogenic viruses.

, Virology, Vol: 624

Comparative 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.

Journal article

Debabèche NB, Wagner M, Jiang Q, Feist F, Bismarck Aet al., 2026,

Cellulose sandwich composites with tube-reinforced foam cores.

, Carbohydr Polym, Vol: 389

Lightweight 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.

Journal article

Ruiz-Sanchis D, Ledesma-Amaro R, 2026,

Evolutionary engineering of synthetic microbial consortia in bioproduction

, Current Opinion in Biotechnology, Vol: 101, ISSN: 0958-1669

Microbial 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 article

Palanivel M, Narayana JK, Chotirmall SH, 2026,

Axial Connectivity of the Lung Microbiome: A Review of Interorgan Crosstalk.

, Compr Physiol, Vol: 16

The classic organ-centric model of human physiology is rapidly giving way to a unified approach embracing the human body as an integrated network of bidirectional interorgan communication. The human microbiome serves as a fundamental mediator of this shift, regulating immune homeostasis, barrier integrity and metabolic signaling across organs. While the lung maintains a characteristic low-biomass microbiome in dynamic equilibrium, any disruption primes local and systemic immune responses contributing to disease. Beyond the well-described gut-lung axis, crosstalk between the lung and other distal organ systems is lesser recognized; however, increasingly acknowledged as a key under-appreciated contributor to respiratory disease including extrapulmonary complications. This review synthesizes current established evidence on axial connectivity of the lung microbiome across the gut, brain, skin, heart, kidney, and liver, and finds that such crosstalk is predominantly, though not exclusively gut-mediated. Direct lung-organ interactions are described for several axes; however, they remain preliminary. Across these lung-axial systems, common pathophysiological mechanisms emerge, including dysbiosis-induced depletion of microbial metabolites, immunomodulation, and barrier perturbations, all linking pulmonary disease with neuroinflammation, gastrointestinal deficits, and cardiac, renal, hepatic, and dermatological abnormalities. We assess how therapeutic modulation of interorgan systems offers promising avenues for improved risk stratification and novel therapeutics. Recognizing microbiome-mediated pulmonary-organ crosstalk represents an emerging conceptual framework in respiratory medicine, repositioning microbial communities as key modulators of extrapulmonary disease.

Journal article

Cotenescu D-I, Burgstaller C, Bismarck A, 2026,

Unidirectional carbon fibre reinforced polyetherimide: Pilot-scale wet powder impregnation and critical composite properties

, Journal of Thermoplastic Composite Materials, ISSN: 0892-7057

<jats:p> High-performance thermoplastic composites are increasingly favoured over traditional thermosets due to their superior toughness, faster processing without complex curing processes, lower health risks, and potential recyclability. Among thermoplastics, amorphous polyetherimide (PEI) offers an attractive set of thermal and mechanical properties compared to semi-crystalline alternatives such as poly(ether-ether-ketone) but at a lower cost. Besides thermal and physical characteristics of PEI, single fibre model composite properties, we present a pilot-scale wet powder impregnation route for manufacturing unidirectional (UD) carbon fibre-reinforced PEI composite tapes with a fibre volume fraction of 58%, tensile load of 1462 ± 72 N and modulus 109 ± 2.3 GPa. The consolidated laminates had a density of 1.56 g/cm <jats:sup>3</jats:sup> and a void content of 1.6%. UD CF/PEI composites had a short beam shear strength of 74 ± 8 MPa and a compressive strength and modulus of 623 ± 3 MPa and 107 ± 8 MPa, respectively, at room temperature. These properties decreased with increasing temperature to 150°C due to matrix softening. Mode II fracture toughness approached the lower bound of CF/PEEK composites making PEI a promising candidate as a matrix for high-performance composite applications. </jats:p>

Journal article

Shah A, 2026,

International epidemiology of antimicrobial resistance in people living with chronic lung infection

, Thorax, ISSN: 0040-6376

Background: Antimicrobial resistance (AMR) is a global threat for people with chronic lung infection, however international AMR epidemiology in bronchiectasis and Cystic Fibrosis (CF) is poorly characterised. In this study we retrospectively analyse international longitudinal AMR epidemiology in bronchiectasis and CF.Methods: Microbiology data was analysed from 110323 respiratory samples in 19143 individuals with bronchiectasis or CF across 11 cities, 8 countries, 3 continents between 2011-2024. Longitudinal AMR prevalence, multi-drug and extensive-drug resistance (MDR,XDR) and multiple antibiotic resistance (MAR) index was analysed by disease and country. Pilot analysis of concurrent/disjoint resistance in antimicrobial pairs and triplets in regional datasets was performed to inform combination or cyclical antimicrobial choice.Findings: Geographic AMR differences were noted across pathogens in bronchiectasis and CF with increased Pseudomonas aeruginosa resistance in central/southern Europe and increased Klebsiella pneumoniae resistance in Hong Kong. MDR burden was high in emergent pathogens Escherichia coli (CF:MDR-32.6%;XDR-12.4%; Bronchiectasis:MDR-39.2%;XDR-4.9%) and K.pneumoniae (CF:MDR-22.7%;XDR-15.6%; A longitudinal rise in P.aeruginosa AMR was seen in bronchiectasis across 4 centres for antipseudomonal aminoglycosides (p=<0.001;OR/yr:1.44;(95%CI:1.24-1.67)), fluoroquinolones (p=0.002;OR/yr:1.13;(95%CI:1.05-1.23)), cephalosporins (p=0.005;OR/yr:1.17;(95%CI:1.051.30)), penicillins with beta-lactamase inhibitor (p=0.02;OR/yr:1.18;(95%CI:1.03-1.35)) and carbapenems (p=0.048;OR/yr:1.11;(95%CI:1.00-1.23)). Rising longitudinal K.pneumoniae AMR was seen for cephalosporins (p=0.01;OR/yr:1.32;(95%CI:1.06-1.65)) and carbapenems (p=0.04;OR/yr:1.64;(95%CI:1.03-2.62)). Significant increased AMR by MAR index was seen in residual culture-positive CF individuals on triple CFTR modulator therapy (p<0.001). Strong concurrent resistance was noted in bronchiectasis across

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Journal article

Moratto E, Masters-Clark E, Clark AJ, Pachmann A, Murphy CWM, Bindshedler S, Junier P, Stanley CEet al., 2026,

A microfluidic platform reveals the role of liquid movement on the dispersal of <i>Pseudomonas putida</i> via <i>Pythium ultimum</i> hyphal highways

, microLife

<jats:title>Abstract</jats:title> <jats:p>Hyphal networks contribute to the connectivity between discrete soil microbial populations by providing a physical network through unsaturated soil matrixes. This network serves as a scaffold for bacteria to disperse and access previously isolated spaces via the “fungal highway”. As bacteria require a liquid film for flagellar swimming, liquid saturation is a significant limiting factor for their dispersal in soil. The current working hypothesis is that bacteria can utilise thin liquid films associated with fungal or fungal-like hyphae to cross air gaps in soil environments. Studying these interactions at the microbial scale, however, is challenging due to the complex and stochastic “black box” nature of soil environments. Hence, the microfluidic Hyphal Highways Device was developed to accomplish long-term quantification of bacterial dispersal along hyphal networks at single-cell level. Key findings highlight that Pythium ultimum is essential for Pseudomonas putida movement across an unsaturated environment, with mycelial biomass and liquid transport being key factors influencing bacterial dispersal. Additionally, P. putida actively modified the distribution of the transported liquid, increasing liquid patch connectivity. The Hyphal Highways Device provided quantitative insights into hyphal-mediated bacterial dispersal, opening new opportunities to study microscale interactions that shape microbial dynamics in natural and agricultural soils.</jats:p>

Journal article

Bidartondo M, 2026,

MycorrhizaTracer: a bioinformatic pipeline for fungi and plant classification of Sanger DNA sequences

, Biodiversity Data Journal, ISSN: 1314-2828

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International epidemiology of antimicrobial resistance in people living with chronic lung infection

MycorrhizaTracer: a bioinformatic pipeline for fungi and plant classification of Sanger DNA sequences

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