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Huisman, J. S.

Publications and source records attributed to Huisman, J. S..

10 recordsLinked to original sources

Growth rate and yield are not constrained by a trade-off in microbes

Ecological theory traditionally posits widespread trade-offs in organismal growth, survival, and reproduction. One core trade-off is the relation between maximum intrinsic growth rate (r) and carrying capacity (K), proposed as a key mechanism explaining species coexistence and the maintenance of biodiversity. To quantify how r relates to K in microbes, we analyzed more than 70,000 microbial growth curves in dozens of media conditions. In this set, we observed a strong positive correlation between r and K, challenging classic life-history expectations of a trade-off. This unexpected "trade-up" can be recovered by a model assuming a non-zero maintenance cost in cells. The model predicts a stronger trade-up under stress conditions that reduce growth rate, consistent with empirical data showing that salinity stress strengthens the trade-up. We also found that community assembly weakens but does not eliminate this positive r-K relationship. The robust growth-yield trade-up between species contrasts with patterns within species. Single-gene knockout datasets in Escherichia coli and budding yeast show no or only weak r-K relationships. Together, our results suggest that the lack of strong trade-offs between growth rate and carrying capacity may be widespread across species, emphasizing the importance of alternative trade-offs and coexistence mechanisms beyond the classical r-K framework.

ecology↗

Transfer potential of F-like plasmids in Escherichia coli differs by animal environment

Plasmids play a key role in the spread of virulence and antimicrobial resistance genes to new genetic backgrounds. Genetic variation in the transfer operon, which contain the genes responsible for conjugation, can lead to substantial differences in transfer potential even between closely related plasmids. However, it is not clear how much genetic diversity there is in transfer operons of natural bacterial populations. Here, we analyse the prevalence and transfer potential of F-like plasmids, a clinically important family of plasmids in Enterobacteriaceae, by searching for the presence of essential conjugation genes in 1200 Escherichia coli genomes isolated from three livestock-associated environments. We find that the fraction of F-like transfer operons that are functionally complete was significantly higher in poultry than in bovine and swine associated bacteria. This difference was not captured in methods that use the presence of replication genes to estimate plasmid prevalence. Confounders such as the phylogenetic relatedness of E. coli or the presence of antibiotic resistance could not explain these significant differences in transfer potential. Instead, it seems the poultry environment selects for plasmids with high transfer potential, as it also contained more conjugative plasmid types per isolate. While we find environment specific differences in overall plasmid frequency, patterns of transfer gene presence/absence were similar across the three environments. Regulatory and exclusion genes are the exception to this pattern, suggesting environment specific modulation of transfer rates. This highlights the use of genomic data to uncover environment specific differences in plasmid prevalence and transfer potential, revealing the selection pressures shaping horizontal gene transfer in these environments.

microbiology↗

Microbial communities demonstrate robustness in stressful environments due to predictable composition shifts

Environmental stress reduces species growth rates, but its impact on the function of microbial communities is less clear. Here, we experimentally demonstrate that increasing salinity stress shifts community composition towards species with higher growth rates. As a result, the mean community growth rate is more robust to increasing stress than the growth of individual species. We show this by propagating natural aquatic communities at multiple salinities and mapping the observed diversity onto the measured salinity performance curves of >80 bacterial isolates. We further validate these results with pairwise species competitions and in metagenomic data of natural communities sampled from estuarine environments. A Lotka-Volterra model including mortality and salinity-dependent growth rates recapitulates the observed robustness of community growth sustained by more abundant faster growers at high salinity. These results extend to other environmental stressors and point to fundamental mechanisms with which communities maintain growth despite deteriorating conditions.

microbiology↗

The effect of sequencing and assembly on the inference of horizontal gene transfer on chromosomal and plasmid phylogenies

The spread of antibiotic resistance genes on plasmids is a threat to human and animal health. Phylogenies of bacteria and their plasmids contain clues regarding the frequency of plasmid transfer events, as well as the co-evolution of plasmids and their hosts. However, whole genome sequencing data from diverse ecological or clinical bacterial samples is rarely used to study plasmid phylogenies and resistance gene transfer. This is partially due to the difficulty to extract plasmids from short-read sequencing data. Here, we use both short- and long-read sequencing data of 24 clinical extended-spectrum {beta}-lactamase producing Escherichia coli to estimate chromosomal and plasmid phylogenies. We compare the impact of different sequencing and assembly methodologies on these phylogenies and on the inference of horizontal gene transfer. We find chromosomal phylogenies can be estimated robustly with all methods, whereas plasmid phylogenies have more variable topology and branch lengths across the methods used. Specifically, hybrid methods that use long reads to resolve short-read assemblies (HybridSPAdes and Unicycler) perform better than those that started from long-reads during assembly graph generation (Canu). In contrast, the inference of plasmid and antibiotic resistance gene transfer using a parsimony-based criterion is mostly robust to the choice of sequencing and assembly method.

bioinformatics↗

Plasmid co-infection: linking biological mechanisms to ecological and evolutionary dynamics

As infectious agents of bacteria and vehicles of horizontal gene transfer, plasmids play a key role in bacterial ecology and evolution. Plasmid dynamics are shaped not only by plasmid-host interactions, but also by ecological interactions between plasmid variants. These interactions are complex: plasmids can co-infect the same host cell and the consequences for the co-resident plasmid can be either beneficial or detrimental. Many of the biological processes that govern plasmid co-infection-from systems to exclude infection by other plasmids to interactions in the regulation of plasmid copy number per cell-are well characterised at a mechanistic level. Modelling plays a central role in translating such mechanistic insights into predictions about plasmid dynamics, and in turn, the impact of these dynamics on bacterial evolution. Theoretical work in evolutionary epidemiology has shown that formulating models of co-infection is not trivial, as some modelling choices can introduce unintended ecological assumptions. Here, we review how the biological processes that govern co-infection can be represented in a mathematical model, discuss potential modelling pitfalls, and analyse this model to provide general insights into how co-infection impacts eco-evolutionary outcomes. In particular, we demonstrate how beneficial and detrimental effects of co-infection give rise to frequency-dependent selection.

microbiology↗

Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation promote within-host plasmid transfer

Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut-luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic-therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. ESBL plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.

evolutionary biology↗

Cooperative virulence can emerge via horizontal gene transfer but is stabilized by transmission

Intestinal inflammation fuels Salmonella Typhimurium (S.Tm) transmission despite a fitness cost associated with the expression of virulence. Cheater mutants can emerge that profit from inflammation without enduring this cost. Intestinal virulence in S.Tm is therefore a cooperative trait, and its evolution a conundrum. Horizontal gene transfer (HGT) of cooperative alleles may facilitate the emergence of cooperative virulence, despite its instability. To test this hypothesis, we cloned hilD, coding for a master regulator of virulence, into a conjugative plasmid that is highly transferrable during intestinal colonization. We demonstrate that virulence can emerge by hilD transfer between avirulent strains in vivo. However, this was indeed unstable and hilD mutant cheaters arose within a few days. The timing of cheater emergence depended on the cost. We further show that stabilization of cooperative virulence in S.Tm is dependent on transmission dynamics, strengthened by population bottlenecks, leading cheaters to extinction and allowing cooperators to thrive.

evolutionary biology↗

Evolutionary mechanisms that determine which bacterial genes are carried on plasmids

The evolutionary pressures that determine the location (chromosomal or plasmid-borne) of bacterial genes are not fully understood. We investigate these pressures through mathematical modelling in the context of antibiotic resistance, which is often found on plasmids. Our central finding is that gene location is under positive frequency-dependent selection: the higher the frequency of one form of resistance compared to the other, the higher its relative fitness. This can keep moderately beneficial genes on plasmids, despite occasional plasmid loss. For these genes, positive frequency-dependence leads to a priority effect: whichever form is acquired first - through either mutation or horizontal gene transfer - has time to increase in frequency and thus become difficult to displace. Higher rates of horizontal transfer of plasmid-borne than chromosomal genes therefore predict moderately beneficial genes will be found on plasmids. Gene flow between plasmid and chromosome allows chromosomal forms to arise, but positive frequencydependent selection prevents these from establishing. Further modelling shows this effect is particularly pronounced when genes are shared across a large number of species, suggesting antibiotic resistance genes are often found on plasmids because they are moderately beneficial across many species. We also revisit previous theoretical work - relating to the role of local adaptation in explaining gene location and to plasmid persistence - in light of our findings. Impact StatementBacterial genes can either reside on the chromosome or on plasmids, extra-chromosomal genetic structures which can be transferred from cell to cell. The distribution of genes between plasmid and chromosome is not random: certain types of genes are particularly likely to be plasmid-associated. This includes a number of clinically important traits, such as antibiotic resistance and virulence factors. The evolutionary mechanisms that give rise to this pattern are not well understood. Plasmids are occasionally lost during cell replication and thus less reliably inherited than the chromosome, and genes are free to transition between plasmid and chromosome: so what keeps genes on plasmids? We address this question using a mathematical model. The key prediction from our model is that the relative fitness of chromosomal and plasmid-borne genes depends on their relative frequencies ( positive frequency-dependent selection). In other words, the fitness of a plasmid-borne gene will be higher in a population in which the chromosomal gene is rare (and vice-versa). This positive-frequency dependence can keep moderately beneficial genes on plasmids, despite occasional plasmid loss. This leads to a priority effect: whichever form of the gene (i.e. plasmid-borne or chromosomal) is acquired first has time to increase in frequency and thus become difficult to displace. Therefore, the relative rate of acquiring the gene on the plasmid vs the chromosome predicts where the gene will be found. Further modelling shows this effect is particularly pronounced when genes are beneficial across a large number of species. All together, the hypothesis that emerges from our work is that plasmid-borne genes are moderately beneficial; functional across a large number of species; and rarely acquired through chromosomal mutation. We suggest traits like antibiotic resistance are often found on plasmids because these genes commonly fulfill these criteria.

evolutionary biology↗

Estimating the rate of plasmid transfer in liquid mating cultures

Plasmids are important vectors for the spread of genes among diverse populations of bacteria. However, there is no standard method to determine the rate at which they spread horizontally via conjugation. Here, we compare commonly used methods on simulated and experimental data, and show that the resulting conjugation rate estimates often depend strongly on the time of measurement, the initial population densities, or the initial ratio of donor to recipient populations. Differences in growth rate, e.g. induced by sub-lethal antibiotic concentrations or temperature, can also significantly bias conjugation rate estimates. We derive a new end-point measure to estimate conjugation rates, which extends the well-known Simonsen method to include the effects of differences in population growth and conjugation rates from donors and transconjugants. We further derive analytical expressions for the parameter range in which these approximations remain valid. We present an easy to use R package and web interface which implement both new and previously existing methods to estimate conjugation rates. The result is a set of tools and guidelines for accurate and comparable measurement of plasmid conjugation rates. HighlightsO_LIWe present an R package and Shiny app to estimate conjugation rates from experimental data C_LIO_LIWe highlight the diversity of existing measures used to estimate conjugation rates C_LIO_LIWe show these measures are biased for populations with differing growth and conjugation rates from donors or transconjugants C_LIO_LIWe develop a new end-point measure which accounts for such differences in growth and conjugation rates C_LI

microbiology↗

Extended-spectrum beta-lactamase antibiotic resistance plasmids have diverse transfer rates and can be spread in the absence of selection

Horizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasmids in the absence of antibiotics. We showed that clinical Escherichia coli strains natively associated with ESBL-plasmids conjugate efficiently with three distinct E. coli strains and one Salmonella enterica serovar Typhimurium strain, reaching final transconjugant frequencies of up to 1% within 24 hours in vitro. The variation of final transconjugant frequencies varied among plasmids, donors and recipients and was better explained by variation in conjugative transfer efficiency than by variable clonal expansion. We identified plasmid-specific genetic factors, specifically the presence/absence of transfer genes, that influenced final transconjugant frequencies. Finally, we investigated plasmid spread within the mouse intestine, demonstrating qualitative agreement between plasmid spread in vitro and in vivo. This suggests a potential for the prediction of plasmid spread in the gut of animals and humans, based on in vitro testing. Altogether, this may allow the identification of resistance plasmids with high spreading potential and help to devise appropriate measures to restrict their spread.

microbiology↗