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Hauser, A.

Publications and source records attributed to Hauser, A..

2 recordsLinked to original sources
bioRxiv2021

Urinary Metabolomics from a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

BackgroundPolymyxin B remains an important antimicrobial against multi-drug resistant bacteria; however, kidney injury is often a treatment limiting event with kidney failure rates that range from 5-13%. MethodsSamples were obtained from a previously conducted study of male Sprague-Dawley rats that received dose fractionated polymyxin B (12 mg/kg/day subcutaneously) once daily (QD), twice daily (BID), and thrice daily (TID) for three days. In the original study, urinary biomarkers and kidney histopathology scores were determined. Urine was sampled daily and analyzed for urinary metabolites via 1H NMR analysis. Unsupervised Principal Components Analysis was applied for exploratory data analysis to identify trends and outliers in the spectral data. Then, supervised Orthogonal Partial Least Square Discriminant Analysis was applied to classify the samples collected in different days and identify metabolic differences during the treatment. Metabolomes were compared across study groups (i.e. those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. ResultsA total of 27 rats contributed 77 urinary samples; n=25 rats were included that were treated with Polymyxin B and n=2 received saline. Pre-dosing samples clustered well and were characterized by higher amounts of citrate, 2-oxoglutarate, and Hippurate. On day 1 post treatment, day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite significantly increased in both BID and TID compared to QD group. Taurine on day 1 correlated with increasing histopathology scores (Spearmans rho = 0.4167, P=0.038) and KIM-1 (Spearmans rho =0.4052, P=0.036); whereas KIM-1 on day one and day 3 did not reach significance with histopathology (Spearmans rho = 0.3248, P=0.11 and Spearmans rho = 0.3739, P=0.066). ConclusionPolymyxin B causes increased amounts of urinary taurine on day 1 which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.

pharmacology and toxicology↗
bioRxiv2021

Retrotransposons as pathogenicity factors of the plant pathogenic fungus Botrytis cinerea

BackgroundRetrotransposons are genetic elements inducing mutations in all domains of life. Despite their detrimental effect, retrotransposons become temporarily active during epigenetic reprogramming and cellular stress response, which may accelerate host genome evolution. In fungal pathogens, a positive role has been attributed to retrotransposons when shaping genome architecture and expression of genes encoding pathogenicity factors; thus, retrotransposons are known to influence pathogenicity. ResultsWe here uncovered a hitherto unknown role of fungal retrotransposons as being pathogenicity factors, themselves. Studying the aggressive fungal plant pathogen Botrytis cinerea, that is known to deliver some long-terminal repeat (LTR) deriving regulatory trans-species small RNAs (BcsRNAs) into plant cells to suppress host gene expression for infection we found that naturally occurring, less aggressive B. cinerea strains possess considerably lower copy numbers of LTR retrotransposons and had lost retrotransposon BcsRNA production. By a transgenic proof-of-concept approach, we reconstituted retrotransposon expression in a BcsRNA-lacking B. cinerea strain, which resulted in enhanced aggressiveness in a retrotransposon and BcsRNA expression-dependent manner. Moreover, retrotransposon expression in B. cinerea led to suppression of plant defence-related genes during infection. ConclusionsWe propose that retrotransposons are pathogenicity factors that manipulate host plant gene expression by encoding trans-species BcsRNAs. Taken together, the novelty that retrotransposons are pathogenicity factors will have general impact on studies of host-microbe interactions and pathology.

genomics↗