Biology subjects

Windels, E. M.

Publications and source records attributed to Windels, E. M..

4 recordsLinked to original sources

bioRxiv2025

Phylodynamic estimation of the within-host mutation rate of extended-spectrum beta-lactamase-producing Enterobacterales

Despite their clinical relevance, the within-host evolution of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) is still poorly understood. To estimate the within-host mutation rates of ESBL-producing Escherichia coli and Klebsiella pneumoniae species complex, we fitted phylodynamic models to genomic sequence data of longitudinally collected rectal swabs from 64 colonized hospital patients. We estimated an average within-host mutation rate of 7.71e-07 [4.60e-07,1.10e-06] mutations/site/year for E. coli and 4.20e-07 [1.57e-07,7.14e-07] mutations/site/year for K. pneumoniae species complex, with limited variation observed across patients and sequence types. These estimates are presumably the most accurate reported so far and are useful for future epidemiological and evolutionary studies. Impact statementUnderstanding the within-patient mutation rates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae species complex is critical for elucidating their evolutionary dynamics and transmission potential. In this study, we employed Bayesian phylodynamic models to analyze longitudinal isolates collected over a 10-year period from hospitalized patients. Our findings reveal limited variability in mutation rates across patients and sequence types, suggesting evolutionary stability within these pathogens in hospital settings. This work provides new insights into the persistence and evolutionary dynamics of ESBL-PE, offering valuable guidance for antimicrobial resistance surveillance and infection prevention strategies. Data summaryThe data used in this study are publicly available in the NCBI database under the BioProject number PRJNA910977. Supporting metadata are provided in Appendix 1. The code for the phylodynamic analyses, including the BEAST2 XML files, is available at https://github.com/EtthelWindels/esbl-pe_mutation. All supporting data, code and protocols have been provided within the article, supplementary data files or public repositories.

genomics↗

bioRxiv2024

Onset of infectiousness explains differences in transmissibility across Mycobacterium tuberculosis lineages

Mycobacterium tuberculosis complex (MTBC) lineages show substantial variability in virulence, but the epidemiological consequences of this variability have not been studied in detail. Here, we aimed for a lineage-specific epidemiological characterization by applying phylodynamic models to genomic data from different countries, representing the most abundant MTBC lineages. Our results show that all lineages are associated with similar durations and levels of infectiousness, resulting in similar reproductive numbers. However, L1 and L6 are associated with a delayed onset of infectiousness, leading to longer periods between subsequent transmission events. Together, our findings highlight the role of MTBC phylogenetic diversity in tuberculosis disease progression and transmission.

genomics↗

bioRxiv2023

HIV co-infection is associated with reduced Mycobacterium tuberculosis transmissibility in sub-Saharan Africa

Persons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection with Mycobacterium tuberculosis (Mtb). However, it has remained unclear how HIV co-infection affects subsequent Mtb transmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on the Mtb transmission dynamics from sequence data. We applied our model to four Mtb genomic datasets collected in sub-Saharan African countries with a generalized HIV epidemic. Our results confirm that HIV co-infection is a strong risk factor for developing active TB. Additionally, we demonstrate that HIV co-infection is associated with a reduced effective reproductive number for TB. Stratifying the population by CD4+ T-cell count yielded similar results, suggesting that, in this context, CD4+ T-cell count is not a better predictor of Mtb transmissibility than HIV infection status. Together, our genome-based analyses complement observational household studies, and firmly establish the negative association between HIV co-infection and Mtb transmissibility. Author summaryMany sub-Saharan African countries have seen a considerable rise in TB incidence since the introduction of HIV, suggesting a strong interaction between HIV and TB epidemics. HIV infection is recognized as an important risk factor for developing TB, but the contribution of HIV-infected TB patients to further Mtb transmission is poorly understood. In this study, we analyzed four sets of Mtb genomic sequences collected in different countries, including sequences from HIV-negative and HIV-positive TB patients. We applied a phylodynamic model to these sequences, aimed at inferring transmission dynamics within and between different host populations. While our findings support that HIV is a strong risk factor for TB, we show that HIV-positive TB patients generate a significantly lower number of secondary TB cases than HIV-negative patients. This suggests that HIV-positive patients often act as sinks in Mtb transmission chains, while HIV-negative patients are a major source of transmission.

microbiology↗

bioRxiv2019

Isolation of persisters enabled by ss-lactam-induced filamentation reveals their single-cell awakening characteristics

When exposed to lethal doses of antibiotics, bacterial populations are most often not completely eradicated. A small number of phenotypic variants, defined as persisters, are refractory to antibiotics and survive treatment. Despite their involvement in relapsing infections caused by major pathogens, processes determining phenotypic switches from and to the persister state largely remain elusive. This is mainly due to the low frequency of persisters in a population and the lack of reliable persistence markers, both hampering studies of persistence at the single-cell level. Problematically, existing methods to enrich for persisters result in samples with very low persister densities and/or a too high abundance of other cell types. Here we present a novel and highly effective persister isolation method involving cephalexin, an antibiotic that induces extensive filamentation of susceptible cells. We show that antibiotic-tolerant cells can easily be separated by size after a short cephalexin treatment, and that the isolated cells are genuine persisters. We used our isolation method to monitor persister outgrowth at the single-cell level in a microfluidic device, thereby conclusively demonstrating that awakening is a stochastic phenomenon. We anticipate that our novel approach can have far-reaching consequences in the persistence field, by allowing single-cell studies at a much higher throughput than previously reported.

microbiology↗