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Morel-Journel, T.

Publications and source records attributed to Morel-Journel, T..

10 recordsLinked to original sources

Chromosomal integration of blaCTX-M redefines the evolutionary trajectory of antibiotic resistance in E. coli through lineage-structured expansion

The global CTX-M pandemic is considered a plasmid-driven phenomenon, yet chromosomal integration of blaCTX-M has been reported in various settings. Screening 451,174 publicly available E. coli genomes and retaining 2,269 CTX-M-E. coli long-read or hybrid assemblies, we found that 33.5% carried at least one chromosomally integrated blaCTX-M. Chromosomal integration was strongly structured by E. coli lineage and CTX-M variant, reaching 68.5% in ST38 and 43.9% in ST131. In the latter, integration rates varied between subclades with modelling, suggesting recent acceleration within the ST131-C2 subclade. Additional resistance genes were frequently co-integrated with blaCTX-M (33%), with architectures largely inherited from plasmid-borne structures. Integrations were mainly ISEcp1- or IS26-mediated (77.3% and 18.9%, respectively) and occurred across the entire E. coli chromosome without spared zones. blaCTX-M chromosomal integration is a widespread, lineage-structured component of the CTX-M pandemic, providing stable vertical inheritance that complements or may supplant plasmid-mediated dissemination in successful ESBL-E. coli clones.

microbiology↗

Quantifying the mechanisms of vaccine-induced serotype replacement in Streptococcus pneumoniae using genome-informed modelling

Streptococcus pneumoniae is a colonizer of the childs nasopharynx and a leading cause of invasive pneumococcal disease (IPD). Despite widespread use of pneumococcal conjugate vaccines, recent rebounds in IPD incidence have coincided with serotype replacement. Whether this phenomenon is driven by the replacement of serotypes within lineages or the replacement of the lineages themselves is unclear. Here, we quantified the relative contribution of these two mechanisms to serotype replacement in carriage and their consequences for IPD. We combined nationwide longitudinal surveillance of carriage and IPD in children from 2002 to 2023 with whole-genome sequencing. Observed lineage-specific carriage rates across PCV-related periods were fitted with polynomial logistic regression and compared with two counterfactual scenarios, each isolating one mechanism with: (i) fixed serotype composition within varying lineages and (ii) serotype shifts within fixed lineage carriage rates over time. Carriage dynamics were consistent with an 82% contribution of serotype shifts within persistent lineages. Estimates of serotype-specific IPD incidence derived from this predominant scenario correlated with observed IPD trends. These findings quantify the dominant role of serotype replacement within persistent lineages, disentangling the vaccine-driven adaptive history of S. pneumoniae.

microbiology↗

Influence of iron uptake systems on cefiderocol activity in Escherichia coli: at the crossroads of antibiotic resistance and virulence

Cefiderocol (FDC) is a new siderophore-conjugated cephalosporin that enters the periplasm via iron transport systems. However, the specific contribution of individual iron uptake pathways to FDC activity remains unclear. We investigated the role of 12 iron acquisition systems using several Escherichia coli strain collections. FDC MICs were determined in iron-depleted and iron-supplemented media for E. coli mutants (Keio and pathogenic island [PAI]-deleted collections) and for clinical wild-type or TEM-producing E. coli (WT/TEM-Ec) and NDM-producing (NDM-Ec) isolates. The distribution of iron uptake genes was assessed in these isolates. In addition, fec operon prevalence and genomic location were investigated in E. coli genomes from EnteroBase and RefSeq databases. Among Keio and 536-PAI-deleted mutants, only {Delta}cirA and {Delta}fiu (enterobactin system) showed increased FDC MICs (8- and 3-fold, respectively), while {Delta}fecA and {Delta}fecB had lower MICs (3-fold decrease). The fec operon, a known extraintestinal virulence factor, was significantly more prevalent in isolates with FDC MICs above median than in those with MICs below (94% vs. 38% in WT/TEM-Ec; 100% vs. 0% in NDM-Ec). According to EUCAST breakpoints, 66.7% of fec-positive NDM-Ec were resistant to FDC while none of the fec-negative were. The fec operon was found in 46.5% of E. coli genomes, including virulent clones (ST131, 77%) and was mostly chromosome-borne (99%). Plasmid-borne fec closely resembled that of Enterobacter hormaechei, suggesting interspecies transfer. Our findings highlight the role of Fec in reducing FDC susceptibility and promoting resistance in NDM-producing E. coli. They challenge the virulence-resistance trade-off demonstrating the liaisons dangereuses between iron and antibiotics.

microbiology↗

Quantifying the effects of antibiotic resistance and within-host competition on strain fitness in Streptococcus pneumoniae

Competition plays a key role in shaping the structure and diversity of bacterial populations. In many clinically important bacterial species, strains compete at multiple scales: at the between-host scale for new hosts to colonise, and at the within-host scale during co-colonisation. Characterising these multiple facets of competition plays an important role in understanding bacterial ecology. This is particularly relevant for antibiotic resistance, where competition between antibiotic-susceptible and resistant strains determines resistance dynamics. In this work, we perform survival analyses on a large longitudinal dataset of Streptococcus pneumoniae carriage to quantify how within-host competition affects the rates of clearance and establishment of pneumococcal strains. We find that the presence of a within-host competitor is associated with a 33% increase in clearance and a 54% reduction in establishment. Priority effects and serotype differences partially predict the outcomes of this within-host competition. Further, we quantify the effects of antibiotic resistance on betweenand within-host components of fitness. Antibiotic consumption is associated with increased clearance rate for both susceptible and resistant strains, albeit to a higher extent in susceptible strains. In the absence of antibiotics, we find some evidence that resistance is associated with increased susceptibility to within-host competition, suggesting a fitness cost of resistance. Overall, our work provides quantitative insights into pneumococcal competition across scales and the role of this competition in shaping pneumococcal epidemiology.

ecology↗

IncC plasmid genome rearrangements influence the vertical and horizontal transmission tradeoff in Escherichia coli

It has been shown that an evolutionary tradeoff between vertical (host growth rate) and horizontal (plasmid conjugation) transmissions contribute to global plasmid fitness. As conjugative IncC plasmids are important for the spread of multidrug resistance (MDR), in a broad range of bacterial hosts, we investigated vertical and horizontal transmissions of two multidrug-resistant IncC plasmids according to their backbones and MDR-region rearrangements, upon plasmid entry into a new host. We observed plasmid genome deletions after conjugation in three diverse natural Escherichia coli clinical strains, varying from null to high number depending on the plasmid, all occurring in the MDR-region. The plasmid burden on bacterial fitness depended more on the strain background than on the structure of the MDR-region, deletions appearing to have no impact. Besides, we observed an increase in plasmid transfer rate, from ancestral host to new clinical recipient strains, when the IncC plasmid was rearranged. Finally, using a second set of conjugation experiments, we investigated the evolutionary tradeoff of the IncC plasmid during the critical period of plasmid establishment in E. coli K-12, by correlating the transfer rates of deleted or non-deleted IncC plasmids and their costs on the recipient strain. Plasmid deletions strongly improved conjugation efficiency with no negative growth effect. Our findings indicate that the flexibility of the MDR-region of the IncC plasmids can promote their dissemination, and provide diverse opportunities to capture new resistance genes. In a broader view, they suggest that the vertical-horizontal transmission tradeoff can be manipulated by the plasmid to improve its fitness.

microbiology↗

Lessons from twenty years of the life of commensal Escherichia coli populations in a human gut

Escherichia coli is an increasingly antibiotic-resistant opportunistic pathogen. Few data are available on its ecological and evolutionary dynamics in its primary commensal niche, the vertebrate gut. Using Illumina and/or Nanopore technologies, we sequenced whole genomes of 210 E. coli isolates from 22 stools sampled during a 20-year period from a healthy man (ED) living in Paris, France. All phylogroups, except C, were represented, with a predominance of B2 (34.3%), followed by A and F (19% each) phylogroups. Thirty-five clones were identified based on their haplogroup and pairwise genomic single nucleotide polymorphism distance and classified in three phenotypes according to their abundance and residence time: 25 sub-dominant/transient (52 isolates), five dominant/transient (48 isolates) and five dominant/resident (110 isolates). Four over five dominant/resident clones belonged to B2 and closely related F phylogroups, whereas sub-dominant/transient clones belonged mainly to B1, A and D phylogroups. The long residence times of B2 clones seemed to be counterbalanced by lower colonization abilities. Clones with larger within-host frequency persisted for longer in the host. By comparing ED strain genomes to a collection of commensal E. coli genomes from 359 French individuals, we identified ED-specific genomic properties including a set of genes involved in a metabolic pathway (mhp cluster) and a very rare antiviral defense island. The E. coli colonization within the gut microbiota was shaped by both the intrinsic properties of the strain lineages, in particular longer residence of phylogroup B2, and the environmental constraints such as diet or phages.

microbiology↗

Persistence-colonization trade-off and niche differentiation enable the coexistence of E. coli phylogroups

Despite extensive literature on the pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal in healthy hosts. Based on two detailed longitudinal datasets on the gut microbiota of healthy adult individuals followed over months to years in France and in the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and the ability to remain in the host (residence). Major E. coli lineages (phylogroups) exhibited similar fitness but a diversity of strategies, from strong colonizers residing for a few days in the gut, to poor colonizers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity resided for longest in hosts. Moreover, the residence time of a strain was reduced more strongly when it competed with other strains of the same phylogroup than of different phylogroups, suggesting niche differentiation between them. To investigate the consequences of the trade-off and niche differentiation for coexistence between strains, we developed a discrete-state Markov model describing the dynamics of E. coli in a population of hosts. We found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms enabling the coexistence of phylogroups over extended periods of time. Our model predicted that a reduction in transmission (e.g. better hygiene) would not alter the balance between phylogroups, while disturbance of the microbiome (e.g. antibiotics) would hinder residents strains such as those of the extra-intestinal pathogenic phylogroup B2.3.

evolutionary biology↗

Colonisation debt: when invasion history impacts current range expansion

Demographic processes that occur at the local level, such as positive density dependence in growth or dispersal, are known to shape population range expansion, notably by linking carrying capacity to invasion speed. As a result of these processes, the advance of an invasion front depends both on populations in the core of the invaded area and on small populations at the edge. While the impact on velocity is easily tractable in homogeneous environment, information is lacking on how speed varies in heterogeneous environment due to density dependence. In this study, we tested the existence of a colonisation debt, which corresponds to the impact of conditions previously encountered by an invasion front on its future advances. Due to positive density dependence, invasions are expected to spread respectively slower and faster, along the gradients of increasing and decreasing carrying capacity, with stronger differences as the gradient slope increases. Using simulated invasions in a one-dimensional landscape with periodically varying carrying capacity, we confirmed the existence of the colonisation debt when density-dependent growth or dispersal was included. Additional experimental invasions using a biological model known to exhibit positive density-dependent dispersal confirmed the impact of the carrying capacity of the patch behind the invasion front on its progression, the mechanism behind the colonisation debt.

ecology↗

Rewiring cattle movements to limit infection spread

The cattle tracing databases set up over the past decades in Europe have become major resources for representing demographic processes of livestock and assessing potential risk of infections spreading by trade. The herds registered in these databases are nodes of a network of commercial movements, which can be altered to lower the risk of disease transmission. In this study, we develop an algorithm aimed at reducing the number of infected animals and herds, by rewiring specific movements responsible for trade flows from high- to low-prevalence herds. The algorithm is coupled with a generic computational model describing infection spread within and between herds, based on data extracted from the French cattle movement tracing database (BDNI). This model is used to simulate a wide array of infections, with either a recent outbreak (epidemic) or an outbreak that occurred five years earlier (endemic), on which the performances of the rewiring algorithm are explored. Results highlight the effectiveness of rewiring in containing infections to a limited number of herds for all scenarios, but especially if the outbreak is recent and if the estimation of disease prevalence is frequent. Further analysis reveal that the key parameters of the algorithm affecting infection outcome vary with the infection parameters. Allowing any animal movement from high to low-prevalence herds reduces the effectiveness of the algorithm in epidemic settings, while frequent and fine-grained prevalence assessments improve the impact of the algorithm in endemic settings. According to our results, our approach focusing on a few commercial movements is expected to lead to substantial improvements in the control of a targeted disease, although changes in the network structure should be monitored for potential vulnerabilities to other diseases. Due to its generality, the developed rewiring algorithm could be applied to any network of controlled individual movements liable to spread disease.

zoology↗

When higher carrying capacities lead to faster propagation

This preprint has been reviewed and recommended by Peer Community In Ecology (https://dx.doi.org/10.24072/pci.ecology.100004). Finding general patterns in the expansion of natural populations is a major challenge in ecology and invasion biology. Classical spatio-temporal models predict that the carrying capacity (K) of the environment should have no influence on the speed (v) of an expanding population. We tested the generality of this statement with reaction-diffusion equations, stochastic individual-based models, and microcosms experiments with Trichogramma chilonis wasps. We investigated the dependence between K and v under different assumptions: null model (Fisher-KPP-like assumptions), strong Allee effects, and positive density-dependent dispersal. These approaches led to similar and complementary results. Strong Allee effects, positive density-dependent dispersal and demographic stochasticity in small populations lead to a positive dependence between K and v. A positive correlation between carrying capacity and propagation speed might be more frequent than previously expected, and be the rule when individuals at the edge of a population range are not able to fully drive the expansion.

ecology↗