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Foerster, C.

Publications and source records attributed to Foerster, C..

3 recordsLinked to original sources

Bridging disciplines towards wastewater-based surveillance of antimicrobial resistance: frequency, local dynamics, and genomic characteristics of carbapenemase-producing Klebsiella pneumoniae

The World Health Organization (WHO) has designated carbapenemase-producing Klebsiella pneumoniae (CP-KP) as a critical priority pathogen due to its increasing importance for human health. As wastewater-based surveillance (WBS) is discussed as a complementary tool for classical systems regarding hazard forecasting and early-warning, we designed a "wet-lab to genomics" workflow to target CP-KP in raw influent wastewater samples to support method development processes across different scientific disciplines. The CP-KP screening workflow was set up based on membrane filtration, selective chromogenic media for selective cultivation and the modified carbapenem inactivation method (mCIM) for confirming carbapenemase-production using 33 samples from four different wastewater treatment plants in North-Eastern Germany. All samples tested positive for CP-KP, with concentrations ranging between 102 and 104 colony-forming units (cfu) per 100 ml across the sample set. As a result, 320 isolates belonged to the Klebsiella, Enterobacter, Citrobacter (KEC)- group, with the majority being identified as KP (n= 297; 93%), including n= 253 (79%) verified CP-KP. Genotypic characterization of CP-KP by PCR revealed the predominance of blaOXA-48-related genes (n= 83) among isolates from all WWTPs. As quality parameters, colony counts for viable Escherichia coli (EC) were employed as a proxy for valid wastewater samples and extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) as indicator for AMR, with cfu/100 ml ranges from 10 to 10 and 102 to 10, respectively. To verify the screening outcome, a subset of 58 CP-KP from two WWTPs were subjected to whole genome sequencing (WGS). As a result, eight different sequence types (STs), i.e., ST147 and ST273 (both: clonal group 147), ST258, ST35, ST15, ST37, ST307, and ST485 were identified. These include clinically relevant STs clustering closest with fecal isolates from Germany when compared with Pathogenwatch-database entries. Moreover, WGS data enabled the identification of antibiotic resistance genes (ARGs), and the detection of closely related isolates within the WWTP dataset.

microbiology↗

Hepatitis C virus replication fitness as a determinant of antiviral therapy outcome

Background and AimsHepatitis C virus (HCV) infections were previously treated with interferon (IFN) but today direct acting antivirals (DAAs) with cure rates >95% are available. DAA treatment failure is primarily attributed to resistance associated mutations (RAMs), often imposing a fitness cost. Interferon treatment outcome was shown to be associated with the interferon sensitivity determining region (ISDR), which is part of the replication enhancing domain (ReED) in non-structural protein (NS) 5A. We found that accumulation of mutations in the ReED was indicative of elevated viral genome replication fitness. This study investigates the impact of HCV replication fitness on antiviral treatment outcomes. MethodsWe utilized chimeric HCV subgenomic replicons containing RAMs and ReED sequences from patients after interferon treatment or DAA failure to assess replication fitness of patient isolates in presence and absence of inhibitors. ResultsReplication fitness did not impact on IFN sensitivity in cell culture but resulted in higher remaining antigen levels for highly replicating variants at a given IFN concentration. Furthermore, we identified ReED variants substantially increasing HCV replication in several patients who failed DAA therapy across different genotypes. High replicator ReEDs rescued the fitness loss caused by RAMs like Y93C/H (NS5A) and S282T (NS5B). While high replication fitness did not intrinsically increase drug sensitivity (IC50), it allowed the virus to sustain robust replication despite antiviral pressure. ConclusionsElevated replication fitness might support interferon treatment due to increased antigen presentation, facilitating adaptive immune responses. Furthermore, ReED mediated increase in replication fitness could contribute to DAA treatment failure by preserving higher replication upon treatment and compensating for RAM associated fitness costs. Thus, patients failing DAA treatment should be monitored for RAMs and ReED mutations.

microbiology↗

Root volatiles in plant-plant interactions I: Characterization of root sesquiterpene emissions from Centaurea stoebe and their effects on other plants

Volatile organic compounds (VOCs) emitted by plant leaves can influence the physiology of neighboring plants. In contrast to interactions above ground, little is known about the role of VOCs in belowground plant-plant interactions. Here, we characterize constitutive root volatile emissions of the spotted knapweed (Centaurea stoebe) and explore the impact of these volatiles on the germination and growth of different sympatric plant species. We show that C. stoebe roots emit high amounts of sesquiterpenes, with estimated release rates of (E)-{beta}-caryophyllene above 3 g g-1 dw h-1. Sesquiterpene emissions show little variation between different C. stoebe populations, but vary substantially between different Centaurea species. Through root transcriptome sequencing, we identify six root-expressed sesquiterpene synthases (TPSs). Two root-specific TPSs, CsTPS4 and CsTPS5, are sufficient to produce the full blend of emitted root sesquiterpenes. Volatile exposure experiments demonstrate that C. stoebe root volatiles have neutral to positive effects on the germination and growth of different sympatric neighbors. Thus, constitutive root sesquiterpenes produced by two C. stoebe TPSs are associated with facilitation of sympatric neighboring plants. The release of root VOCs may thus influence C. stoebe abundance and plant community structure in nature.

plant biology↗