Biology subjects

Horn, M. A.

Publications and source records attributed to Horn, M. A..

5 recordsLinked to original sources

bioRxiv2025

Synergies on many levels: Microbially driven redoxgradients as drivers of greenhouse gas emissions in a pH neutral fen

Pristine northern peatlands store large amounts of carbon and nitrogen which are only slowly released under water-logged conditions due to dominance of anaerobic degradation processes. While different parts of the system such as GHG emissions have been intensively studied in many places, less focus has been paid to the integration of different peat processes. A field course at Puukkosuo fen, a pH-neutral site in northern Finland, aimed to investigate the versatile microbial communities in Puukkosuo fen, assess their metabolic potential and interpret in situ peat and porewater observations based on the context of the detected microbial communities and process potential. Microbial communities harbored microorganisms with aerobic and anaerobic metabolic capabilities for nitrification, denitrification, iron reduction, sulfate reduction, fermentation and methanogenesis. Most probable number counts demonstrated that groups like aerobic and anaerobic heterotrophs, denitrifiers and sulfate reducers where highly abundant, while microcosm incubations highlighted the process potential of different functional groups, especially in surface peat. Measurements of in situ concentrations of process substrates, intermediates or products in peat and porewater indicated that different anaerobic processes were active in anoxic peat layers which synergistically contributed to organic matter degradation in Puukkosuo fen.

microbiology↗

bioRxiv2022

Modeling multiphage-bacteria kinetics to predict phage therapy potency and longevity

Pseudomonas aeruginosa is a frequent cause of life-threatening opportunistic infections in the critically ill and immunocompromised. Its treatment is challenging due to the increasing prevalence of resistance to most conventional antibiotics. Although numerous alternative therapies are currently under investigation, bacteriophage (phage) cocktail therapy appears poised for long-term success. Here, we investigate potency and longevity of individual Pseudomonas phages in cocktail to determine viral co-factors that promote optimal treatment efficacy. We combined in vitro and in silico models to predict sixty-eight treatment permutations with three phages that adsorb symmetrically and asymmetrically when administered singly, double simultaneously, or double sequentially. We showed that simultaneously administering two asymmetrically binding phages with high cell lysis efficiencies improved cocktail potency. Use of a higher-potency cocktail, along with a reduction in the net probability of independent gene mutations was associated with prolonged bacterial suppression. Nevertheless, in vitro we almost always observed evolution of multiphage resistance. Simulations also predict that when combining phages with polar potencies, susceptible host cells are monopolized by the more efficiently replicating phage. Thus, further perpetuating the growth demise of the weaker phage in cocktail. Our mathematical model was used to explore and predict changes in phage and bacterial populations that were difficult to measure experimentally. This framework has many inferential and exploratory uses for clinical investigation such as identifying the most sensitive parameters for phage selection and exploring different treatment regimens. Collectively, our findings attempt to dissect the mechanisms of phage cocktails combating P. aeruginosa infections and highlight the viral co-factors necessary for treatment efficacy.

microbiology↗

bioRxiv2022

Effects of microplastic ingestion on hydrogen production and microbiomes in the gut of the terrestrial isopod Porcellio scaber

Microplastic (MP) pollution is an environmental burden. MP enters food webs via ingestion by macrofauna, including isopods (Porcellio scaber) in terrestrial ecosystems. However, MP-effects on the host and its gut microbiome are largely unknown. We tested the hypothesis that biodegradable (polylactic acid, PLA) and non-biodegradable (polyethylene terephthalate, PET; polystyrene, PS) MP have contrasting effects on P. scaber mediated by changes of the associated gut microbiome. Although the isopods avoided food containing PS, isopod fitness after eight-week MP-exposure was unaffected. Qualitative and quantitative 16S rRNA gene and 16S rRNA analyses of gut microbiomes indicated general MP effects, MP-type specific indicator taxa, and stimulation by PLA compared to MP-free controls. Isopods emitted hydrogen, and its production increased and decreased after PLA-food and PET- or PS-food ingestion, respectively, relative to controls as indicated by microsensor measurements. Gut pH was unaffected by MP. We identified the gut of P. scaber as significant mobile source of reductant for soil microbiomes likely due to Enterobacteriaceae related fermentation activities that were stimulated by lactate generated during PLA-degradation. The findings suggest negative effects of PET and PS on gut fermentation, modulation of isopod hydrogen emissions by MP pollution, and the potential of MP to affect terrestrial food webs.

microbiology↗

bioRxiv2021

Disordered yet functional atrial t-tubules on recovery from heart failure

Transverse (t)-tubules drive the rapid and synchronous Ca2+ rise in cardiac myocytes. The virtual complete loss of atrial t-tubules in heart failure (HF) decreases Ca2+ release. It is unknown if or how atrial t-tubules can be restored and if restored t-tubules are functional. Sheep were tachypaced to induce HF and recovered when pacing was stopped. Serial block face Scanning Electron Microscopy and confocal imaging were used to understand t-tubule ultrastructure and function. Candidate proteins involved in atrial t-tubule recovery were identified by western blot and causality determined using expression studies. Sheep atrial t-tubules reappeared following recovery from HF. Despite being disordered (branched, longer and longitudinally arranged) recovered t-tubules triggered Ca2+ release and were associated with restoration of systolic Ca2+. Telethonin and myotubularin abundance correlated with t-tubule density and altered the density and structure of BIN1-driven tubules in neonatal myocytes. Myotubularin had a greater effect, increasing tubule length and branching, replicating that seen in the recovery atria. Recovery from HF restores atrial t-tubules and systolic Ca2+ and myotubularin facilitates this process. Atrial t-tubule restoration could present a new and viable therapeutic strategy. Brief SummaryThe loss of atrial transverse (t)-tubules and the associated dysfunction in heart failure is reversible and the protein myotubularin plays an important role.

physiology↗

bioRxiv2020

Investigating the impact of combination phage and antibiotic therapy: a modeling study

Antimicrobial resistance (AMR) is a serious threat to global health today. The spread of AMR, along with the lack of new drug classes in the antibiotic pipeline, has resulted in a renewed interest in phage therapy, which is the use of bacteriophages to treat pathogenic bacterial infections. This therapy, which was successfully used to treat a variety of infections in the early twentieth century, had been largely dismissed due to the discovery of easy to use antibiotics. However, the continuing emergence of antibiotic resistance has motivated new interest in the use of phage therapy to treat bacterial infections. Though various models have been developed to address the AMR-related issues, there are very few studies that consider the effect of phage-antibiotic combination therapy. Moreover, some of biological details such as the effect of the immune system on phage have been neglected. To address these limitations, we utilized a mathematical model to examine the role of the immune response in concert with phage-antibiotic combination therapy compounded with the effects of the immune system on the phages being used for treatment. We explore the effect of phage-antibiotic combination therapy by adjusting the phage and antibiotics dose or altering the timing. The model results show that it is important to consider the host immune system in the model and that frequency and dose of treatment are important considerations for the effectiveness of treatment. Our study can lead to development of optimal antibiotic use and further reduce the health risks of the human-animal-plant-ecosystem interface caused by AMR.

microbiology↗