Biology subjects

Koutsokera, A.

Publications and source records attributed to Koutsokera, A..

4 recordsLinked to original sources

bioRxiv2026

Adaptation of Pseudomonas aeruginosa to the lung allograft environment in cystic fibrosis lung transplant recipients

Lung transplantation (LT) is the ultimate treatment option for patients suffering from end stage cystic fibrosis (CF). Most LT-patients, colonized pre-LT by Pseudomonas aeruginosa witness colonization of their non-CF allograft within a few days or weeks post-LT, thereby compromising graft and life expectancy. How P. aeruginosa isolates adapted for years to the specific CF lung environment efficiently colonize and survive in the non-CF allograft environment remains unclear. To address this question, we collected sequential isolates from CF LT-recipients and non-CF LT-recipients and performed phenotypic and genetic analyses of pairs of early and late isolates from LT-patients. We found evidence for mutations compatible with a switch from biofilm to planktonic lifestyle as well as loss of mucoid phenotypes. Hypermutators, characteristic of chronic CF-adapted isolates, were also found in four LT-patients. Their persistence in the non-CF allograft environment suggests a continuous seeding from the sinuses. Our results suggest that in CF LT-recipients efficient colonisation by P. aeruginosa of the allograft implies both adaptation and continuous seeding from the sinuses to the lower respiratory tract.

microbiology↗

bioRxiv2025

Fighting Aspergillus infection using biocontrol bacteria: A proof-of-concept of environmental interference in a translational setting

Aspergillus fungi are opportunistic pathogens that affect millions of people worldwide. Aspergilli produce organic acids to optimize the environmental pH and match the needs of their enzymatic machinery. In this study, we tested the hypothesis that this also occurs during infection. By producing oxalic acid (OA), Aspergillus would manipulate pH during lung infection and thus, interfering with this process could control the pathogen. To test this hypothesis, we assessed in silico the potential for OA production in a wide range of Aspergilli. A genetic marker for AO production was detected in most of the species including prevalent human pathogens. We tested OA production in vitro in four strains of A. niger and A. fumigatus, but only one of the A. niger strains produced OA consistently. For this fungal strain, oxalotrophic bacteria were able to control fungal growth via OA consumption. To translate this observation into a pre-clinical system, increasingly complex experiments were performed. In 3D-cell cultures, A. niger also secreted OA and modified pH and free Ca2+. Co-inoculation of the oxalotrophic bacterium inhibited the development of the fungus. However, biocontrol could not be replicated in Galleria mellonella, which is often used as an infection model. In contrast, the bacterium improved disease score and the absence of oxalate crystals in the lungs in the mouse model. This biocontrol interaction between oxalotrophic bacteria and A. niger represents a paradigm shift in the fight against opportunistic fungal pathogens, where the goal is to render the host environment less permissive to pathogen development One Sentence SummaryDemonstration of biocontrol as a therapeutic concept to combat Aspergillus niger with oxalotrophic bacteria in an animal infection model

microbiology↗

bioRxiv2025

Prevalence of Oxalotrophy in the Human Microbiome

Incomplete degradation of oxalate, a compound commonly found in the diet, can cause disease in humans, particularly of the kidney. Its concentration in the body depends on several factors, one of which is intestinal absorption, which is itself affected by oxalotrophy among enteric bacteria. Oxalotrophy in the human microbiome is poorly known. In this study, we perform a systematic search for the simultaneous presence of the three oxalotrophy genes, namely frc, oxc and oxlT. Thanks to the construction and validation of specific conservation models for all three genes, we were able to search for oxalotrophy in genomes and metagenomes associated with the human digestive tract, oral cavity, and lungs. We report that oxalotrophy - the capacity to use oxalate as a source of energy - is a rare metabolic trait, mostly confined to the gut, and also find evidence that it can be acquired by horizontal gene transfer. By contrast, the capacity for oxalate degradation is more widespread, and two genes responsible for it (frc and oxc) are almost always close together in the genome, suggesting selection pressure.

microbiology↗

bioRxiv2020

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation

There is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combined amplicon sequencing and culturomics to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and established links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, pneumotypes. The predominant balanced pneumotype was characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes were characterized by being either microbiota-depleted, or dominated by potential pathogens, and were linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosytem, human lung function, and clinical stability post-transplant. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/106211v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@1df2be3org.highwire.dtl.DTLVardef@ba839dorg.highwire.dtl.DTLVardef@116f657org.highwire.dtl.DTLVardef@86d8ac_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗