Biology subjects

Kuipers, O.

Publications and source records attributed to Kuipers, O..

8 recordsLinked to original sources

bioRxiv2026

Temporal resource variation promotes growth equalization through alternative plasticity strategies

Evolutionary theory predicts that fluctuating environments favor adaptations that maximize geometric-mean fitness by reducing variance in performance across conditions. We tested this prediction experimentally by evolving the lactic acid bacterium Lactococcus cremoris on the sugars fructose and galactose in density-controlled chemostats under four resource regimes: constant supply of fructose, constant supply of galactose, a constant mixture of both sugars, and a temporally alternating supply of the two. In the absence of temporal variation, trade-offs between fructose and galactose resulted in evolutionary divergence into a fructose specialist and a galactose specialist. In contrast, adaptation to temporal resource variation equalised growth performance on both sugars by increasing its growth rate on galactose and decreasing it on fructose. Interestingly, performance equalization emerged across replicate populations through distinct resource-transition strategies, indicated by differences in resource affinity and growth recovery on fructose and galactose among strains isolated from the evolved populations. Our results show that temporal resource variation selects for variance-minimizing resource adaptations while adopting multiple resource transition strategies, illustrating how distinct modes of metabolic plasticity can yield convergent fitness outcomes.

evolutionary biology↗

bioRxiv2025

Migration load, competition, and metabolic trade-offs shape spatial divergence through eco-evolutionary dynamics

Evolutionary models predict that trade-offs related to resource utilization promote local specialization and diversification in spatially heterogeneous environments. However, diversification is also influenced by ecological feedback mechanisms - such as frequency-dependent resource use - and their interaction with migration. To investigate how spatial variation affects diversification, we conducted an evolution experiment exposing populations of Lactococcus cremoris to divergent selection on two carbon sources: fructose and galactose. Using a continuous culture system, we partitioned these resources into two isolated patches (allopatry), two patches with constant migration between them (parapatry), and one fully-mixed patch (sympatry). Resource specialization and subsequent phenotypic diversification evolved in all treatments, revealing a metabolic trade-off between fructose and galactose utilization. Compared to treatments without migration, spatial variation produced a distinctive temporal pattern: migration initially delayed specialization on galactose but later accelerated it. This temporal pattern emerged from eco-evolutionary feedbacks operating through two mechanisms: (i) early in the experiment, higher population density in the better-suited fructose patch increased the influx of maladapted immigrants into the galactose patch, slowing local adaptation; however, (ii) as strains adapted locally to galactose, population density increased in the galactose patch and density asymmetries weakened. Simultaneously, the competitive ability of immigrants declined as residents became increasingly specialized in their local resources, progressively reducing the effective migration rate and allowing accelerated divergence. Our experiment demonstrates how the likelihood and tempo of spatial divergence depend on the evolvability of phenotypic trade-offs and their dynamic interaction with migration load and population density.

ecology↗

bioRxiv2024

Community context influences the conjugation efficiency of E. coli

In urinary tract infections different bacteria can live in a polymicrobial community, it is unknown how such community members affect the conjugation rate of uropathogenic Escherichia coli. We investigated the influence of the polymicrobial urinary tract infection (UTI) community context on the conjugation rate of E. coli isolates in artificial urine medium. Pairwise conjugation rate experiments were conducted between a donor E. coli strain containing pOXA-48 and six uropathogenic E. coli isolates in the presence and absence of five community members to elucidate their effect on the rate of conjugation. We found that the basal conjugation rates in the absence of community members are genotype dependent. Interestingly, bacterial interactions have an overall positive effect on E. coli conjugation rates. Particularly Gram-positive enterococcal species were found to enhance the conjugation rates of most uropathogenic E. coli isolates. We hypothesize that the nature and co-culture of the interactions is important for these increased conjugation rates in AUM.

ecology↗

bioRxiv2022

High-throughput profiling of drug interactions in Gram-positive bacteria

Drug combinations present a powerful strategy to tackle antimicrobial resistance, but have not been systematically tested in many bacterial species. Here, we used an automated high-throughput setup to profile [~] 8000 combinations between 65 antibacterial drugs in three Gram-positive species: the model species, Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulate previously known drug interactions, but also identify ten times more interactions than previously reported in the pathogen S. aureus, including two synergies that were also effective in multi-drug resistant clinical S. aureus isolates in vitro and in vivo. Interactions were largely species-specific and mostly synergistic for drugs targeting the same cellular process, as observed also for Gram-negative species1. Yet, the dominating synergies are clearly distinct between Gram-negative and Gram-positive species, and are driven by different bottlenecks in drug uptake and vulnerabilities of their cell surface structures. To further explore interactions of commonly prescribed non-antibiotic drugs with antibiotics, we tested 2728 of such combinations in S. aureus, detecting a plethora of unexpected antagonisms that could compromise the efficacy of antimicrobial treatments in the age of polypharmacy. We uncovered even more synergies than antagonisms, some of which we could demonstrate as effective combinations in vivo against multi-drug resistant clinical isolates. Among them, we showed that the antiaggregant ticagrelor interferes with purine metabolism and changes the surface charge of S. aureus, leading to strong synergies with cationic antibiotics. Overall, this exemplifies the untapped potential of approved non-antibacterial drugs to be repurposed as antibiotic adjuvants. All data can be browsed through an interactive interface (https://apps.embl.de/combact/).

microbiology↗

bioRxiv2020

Alternative phage-host interaction in Lactococcus lactis: the carrier state drives rapid evolution of phages

Lactococcus lactis is a lactic acid bacterium widely used as starter culture for the manufacture of fermented milk products like quark, buttermilk and cheese. Bacteriophage infection of starter cultures is one of the biggest causes of fermentation failure and, therefore, lactococcal phages have received great attention from the scientific community in the past decades. In this work we present evidence for the establishment of a carrier state life cycle (CSLC) by a bacteriophage belonging to the c2 species, in the model laboratory strain L. lactis MG1363. Our results show that infection of L. lactis MG1363 with a second, dissimilar, c2 bacteriophage can induce the CSLC phage to enter an active lytic life cycle. The viral progeny obtained after this infection is a mixed population of phages with differences in their genome sequences and host ranges, indicative of an extremely rapid evolution process. We discuss the possible implications of this phage-host interaction, both with respect to bacteriophage evolution and phage adaptation to different hosts. IMPORTANCEOur results broaden the current know-how on the yet poorly investigated phage-host interaction mechanism of CSLC, propose a new bacteriophage evolution mechanism, and demonstrate that the outcome of phage infections is possibly more intricate than presently acknowledged.

evolutionary biology↗

bioRxiv2020

Microbial competition reduces interaction distances to the low {micro}m-range

Metabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 {micro}m-sized metabolite producer, receiver and competitor cells in different spatial structures. We show that receivers cannot interact with producers [~]15 {micro}m away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and created variants of the receiver cells import system, to show that within producer-receiver aggregates even low affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces the interaction distance to the low micrometer-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions.

microbiology↗

bioRxiv2019

Biofilm formation displays intrinsic offensive and defensive features of Bacillus cereus

BackgroundBiofilm formation is a strategy of many bacterial species to adapt to a variety of stresses and has become a part of infections, contaminations or beneficial interactions. We previously observed that B. cereus ATCC 14579 (CECT148), formed a thick biomass of cells firmly adhered to abiotic surfaces.\n\nResultsIn this study, we combined two techniques, RNAseq and iTRAQ mass spectrometry, to demonstrate the profound physiological changes that permit Bacillus cereus to switch from a floating to a sessile lifestyle, to undergo further maturation of the biofilm, and to differentiate into offensive or defensive populations. The rearrangement of nucleotides, sugars, amino acids and energy metabolism lead to changes promoting reinforcement of the cell wall, activation of ROS detoxification strategies or secondary metabolite production, all oriented to defend biofilm cells from external aggressions. However, floating cells maintain a fermentative metabolic status along with a higher aggressiveness against hosts, evidenced by the production of toxins and other virulent factors.\n\nConclusionsWe show that biofilm-associated cells seem to direct the energy to the individual and global defense against external aggressions and competitors. By contrary, floating cells are more aggressive against hosts. The maintenance of the two distinct subpopulations is an effective strategy to face changeable environmental conditions found in the life cycle of B. cereus.

microbiology↗

bioRxiv2017

Glucose limitation in Lactococcus shapes a single-peaked fitness landscape exposing membrane occupancy as a constraint

A central theme in biology is to understand the molecular basis of fitness: which strategies succeed under which conditions; how are they mechanistically implemented; and which constraints shape trade-offs between alternative strategies. We approached these questions with parallel bacterial evolution experiments in chemostats. Chemostats provide a constant environment with a defined resource limitation (glucose), in which the growth rate can be controlled. Using Lactococcus lactis, we found a single mutation in a global regulator of carbon metabolism, CcpA, to confer predictable fitness improvements across multiple growth rates. In silico protein structural analysis complemented with biochemical and phenotypic assays, show that the mutation reprograms the CcpA regulon, specifically targeting transporters. This supports that membrane occupancy, rather than biosynthetic capacity, is the dominant constraint for the observed fitness enhancement. It also demonstrates that cells can modulate a pleiotropic regulator to work around limiting constraints.

genomics↗