Biology subjects

Steiner, U.

Publications and source records attributed to Steiner, U..

5 recordsLinked to original sources

bioRxiv2026

Cost and benefits of gene amplification-mediated antibiotic resistance

Bacteria evolve antibiotic resistance through various mechanisms, including horizontal gene transfer, sequence-altering mutations, and tandem duplications/amplifications in genomic regions that increase the dosage of resistance determinants. This phenomenon, known as gene duplication-amplification (GDA), is a transient and reversible genetic mechanism that allows bacteria to rapidly adapt to antibiotic stress. Due to the unstable nature of amplification, the quantitative relationship between gene copy number, resistance levels, and the associated physiological costs remains poorly defined. Here, we constructed strains with fixed GDA copy numbers in a clinical Enterobacter cloacae strain. Using growth curve and time-kill assays, we show that ceftazidime (CAZ) resistance scales with GDA copy number, but the benefit under selection comes with a growth cost in the absence of antibiotic. Notably, we find that while GDA provides a survival advantage under CAZ pressure, it simultaneously increases susceptibility to rapid killing at supra-MIC concentrations. Our analysis further illustrates that survival is jointly shaped by gene dosage, antibiotic concentration, and exposure time. Together, these results clarify that GDA-mediated resistance is highly context dependent, shaped by trade-offs between resistance benefits and physiological costs.

microbiology↗

bioRxiv2024

Protein aggregation drives cell aging in a size-specific manner in Escherichia coli

Aging, the decline in physiological function over time, is marked by the intracellular accumulation of damaged components. It can be attributed to a trade-off between the investment into organismal maintenance and the production of high-quality offspring, where the parent accumulates damage over time and retains it upon reproduction, while the offspring is rejuvenated. Asymmetric damage partitioning has been observed even in simple unicellular organisms, such as Escherichia coli bacteria, that retain aggregates of misfolded proteins during cell division. However, recent studies presented conflicting evidence on the effect of protein aggregates on fitness, ranging from detrimental effects on cell growth to enhanced stress survival. Here, we show that the decisive factor driving growth decline in E. coli is not the presence of a protein aggregate, but the proportion of the intracellular space occupied by it. By following single-cell E. coli lineages expressing fluorescently labeled DnaK chaperones, we quantified damage accumulation and partitioning across generations in microfluidic devices. Our results suggest that the aggregation of damaged proteins allows cells to keep damage separate from vital processes and compensate for the lost intracellular space by growing to larger sizes. This process results in morphologically asymmetric divisions, a finding that counters the long-assumed symmetry of E. coli cell division. In line with other recent evidence, our findings point to a more complex role of protein aggregation, with implications for our understanding of the cellular mechanisms underlying aging as well as its evolutionary origins.

evolutionary biology↗

bioRxiv2021

Bistable host-pathogen interaction explains varied infection outcomes

Death or survival are the two outcomes of an infection. The development of an infection depends on multiple interplaying factors, including the temporal dynamic of host nutrition, immune response and pathogen proliferation, but how these factors collectively determine the outcome of an infection is less understood. To understand the underlying principle of infection, here, we took a systems approach by developing a simple mathematical model to understand multi-factored host-pathogen interaction. We find that nonlinear interactions feedback between host and pathogens resulting in two distinct trajectories of disease progression. We show that disease progression, measured by the pathogen load, responds in a bistable manner, by either proliferating or eventually being eliminated. We identified key processes accounting for bistability, including hosts resource assimilation, immune response and intrinsic noise. In addition, resource availability, immunity, and pathogen load at the onset of infection are also critical in determining the bistability. We then highlight, by discussing in the light of previous theoretical and experimental work, how our framework provides testable theories for host-pathogen interaction inside the host.

ecology↗

bioRxiv2018

Quantifying genetic, environmental and individual stochastic variability in Plantago lanceolata

Predicting ecological and evolutionary population dynamics requires understanding how genetic and environmental parameters influence variation in survival and reproduction among individuals. However such a focus often neglects the stochastic events that individuals experience throughout their lives that also influence survival and reproduction. With an illustrative example, we quantify and illustrate the influence of such non-selective demographic variability on population dynamics using size-structured matrix models of an experimental population of Plantago lanceolata. Our analysis shows that variation in survival and reproduction among individuals explained by environment, genes, and their interaction was modest compared to the stochastic variation in lifespan and reproduction. We illustrate how expectations on population growth, based on expected lifetime reproduction and generation time, can be misleading when variance in reproduction among individuals of the same genotype (full sibs) was large. Such large within genotype variance can lower population growth, fitness. Our results accompany recent investigations that call for more focus on stochastic variation in survival and reproduction, rather than dismissal of this variation as uninformative noise.

evolutionary biology↗

bioRxiv2017

Parallel progress in perceived age and life expectancy

Human life expectancy continues to rise in most populations. This rise not only leads to longer lives but is also accompanied by improved health at a given age, i.e. we see a reduction of biological age for a given chronological age in recent cohorts. Despite or even because of the diversity of biomarkers of aging, an accurate quantification of a general shift in biological age across time has been challenging. By comparing age perception of images taken in 2001 over a decade, we show that age perception changes substantially across time and parallels the progress in life expectancy. In 2012, people aged 70+ needed to look 2.3 years younger to be rated the same age as in 2002. Our results further suggest that age perception reflects the past life events better than predicts future length of life, i.e. it is written in your face how much you have aged so far, but does not predict well how fast you will age in the future. We draw this conclusion since age perception among elderly paralleled changes in life expectancy at birth but not changes in remaining life expectancies. We illustrate advantages of perceived age as a biomarker of aging and suggest that changes in age perception should be explored for younger age classes to inform on aging processes, including whether aging is delayed or slowed with increasing life expectancy.

epidemiology↗