Biology subjects

Goossens, H.

Publications and source records attributed to Goossens, H..

7 recordsLinked to original sources

bioRxiv2024

Bridging immunotypes and enterotypes using a systems immunology approach

Unveiling the systemic effects of disease and health requires an holistic approach that has mainly revolved around well established, directly determinable molecular relationships such as the protein synthesis cascade and epigenetic mechanisms. In this study, involving 394 individuals, we found direct linkage of branches spanning human biological functions often not studied in conjunction, using clinical data, gut microbial abundances, blood immune cell repertoires, blood transcriptomic and blood T cell receptor data. Contrary to current paradigms, we demonstrate that immunotypes and enterotypes are orthogonal, likely fulfilling distinct roles in maintaining homeostasis, only bridged via the blood transcriptome. We also identified two distinct inflammatory profiles: the first driven by interferon signalling and the other characterised by non-viral, NF-kB and IL-6 markers. Lastly, we present compelling data showing strong associations of the Ruminococcaceae and Christensenellaceae bacteria with a healthy immunotype and transcriptomic pattern, highlighting their potential role in immune health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/625344v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@c6b5eorg.highwire.dtl.DTLVardef@15d0c3forg.highwire.dtl.DTLVardef@1cf29eeorg.highwire.dtl.DTLVardef@1c9ff8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

International and regional spread of carbapenem-resistant Klebsiella pneumoniae in Europe

Klebsiella pneumoniae, an opportunistic pathogen able to cause hospital- and community-acquired infections, is of particular concern due to the active spread of antibiotic resistance genes associated with mobile genetic elements such as plasmids and transposons. Carbapenem-resistant K. pneumoniae (CRKP) exhibit a higher mortality rate than carbapenem-susceptible K. pneumoniae infections. In this COMBACTE-EURECA study, we present genomic data of 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018) and compared these with the previous EuSCAPE collection (2013-2014). All isolates were resistant (EUCAST criteria) to at least one carbapenem antibiotic. We identified 11 clonal complexes (CCs), with most isolates belonging to the high-risk clones CC258, CC101, CC11, and CC307. blaKPC-like was the most prevalent carbapenemase-encoding gene (45%), along with the dominance of the CC258 lineage. Equally, blaOXA-48 had a wide-ranging spread (39%), and blaNDM was present in half of the ST11 isolates representing a particular lineage circulating in Greece. Two carbapenemase genes were found in 38 isolates (5.5%). Through the combination of both EURECA and EuSCAPE collections, we elucidated the evolution of K. pneumoniae high-risk clones circulating in Europe. Dominating clones and their associated carbapenemase genes exhibit relevant regional differences, namely CC258 in Greece, Italy, and Spain, CC101 present in Serbia and Romania and CC14 in Turkiye. Due to the wide expansion of CRKP, genomic surveillance across Europe with projects such as EURECA provides crucial insights for risk mapping at geo-temporal scales and informs necessary adaptions to the local settings for implementation of control strategies.

microbiology↗

bioRxiv2020

Harmonization of whole genome sequencing for outbreak surveillance of Enterobacteriaceae and Enterococci

Whole genome sequencing (WGS), is becoming the facto standard for bacterial typing and outbreak surveillance of resistant bacterial pathogens. We performed a three-center ring trial to assert if inter-laboratory harmonization of WGS is achievable, for this goal. To this end, a set of 30 bacterial isolates comprising of various species belonging to the Enterobacteriaceae and Enterococcus genera were selected and sequenced using the same protocol on the Illumina MiSeq platform in each individual centre. All generated sequencing data was analysed by 1 centre using BioNumerics (6.7.3) for i) genotyping origin of replications & antimicrobial resistance genes, ii) core-genome (cgMLST) for E. coli and K. pneumoniae & whole-genome multi locus sequencing typing (wgMLST) for all species. Additionally, a split k-mer analysis was performed to determine the number of SNPs between samples. A precision of 99.0% and an accuracy of 99.2% was achieved for genotyping. Based on cgMLST, only in 2/27 and 3/15 comparisons a discrepant allele was called between two genomes, for E. coli and K. pneumonia, respectively. Based on wgMLST, the number of discrepant alleles ranged from 0 to 7 (average 1.6). For SNPs, this ranged from 0-11 SNPs (average 3.4). Furthermore, we demonstrate that using different de novo assemblers to analyse the same dataset introduces up to 150 SNPs, which surpasses most thresholds for bacterial outbreaks. This shows the importance of harmonisation of data processing surveillance of bacterial outbreaks. Summarizing, multi-center WGS for bacterial surveillance is achievable, but only if protocols are harmonized.

microbiology↗

bioRxiv2020

Rapid evolution drives the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

It is well established that antibiotic treatment selects for resistance in pathogenic bacteria. However, the evolutionary responses of pathogen populations to antibiotic treatment during infections remain poorly resolved, especially in acute infections. Here we map the evolutionary responses to treatment in high definition through genomic and phenotypic characterization of >100 isolates from a patient with P. aeruginosa pneumonia. Antibiotic therapy (meropenem, colistin) caused a rapid crash of the P. aeruginosa population in the lung, but this decline was followed by the spread of meropenem resistance mutations that restrict antibiotic uptake (oprD) or modify LPS biosynthesis (wbpM). Low fitness strains with high-level meropenem resistance (oprD) were then replaced by high fitness strains with anti-resistance mutations in the MexAB-OprM efflux pump, causing a rapid decline in resistance to both meropenem and a collateral loss of resistance to a broad spectrum of antibiotics. In contrast, we did not observe any evolutionary responses to antibiotic treatment in the intestinal population of P. aeruginosa. Carbapenem antibiotics are key to the treatment of infections caused by Gram negative pathogens, and our work highlights the ability of natural selection to drive both the rapid rise and fall of carbapenem resistance during acute infections.

evolutionary biology↗

bioRxiv2020

Evaluation of a Loop-Mediated Isothermal Amplification assay to detect carbapenemases from Acinetobacter spp. directly from bronchoalveolar lavage fluid

Carbapenem-resistant Acinetobacter spp. mainly Acinetobacter baumannii are frequently causing nosocomial infections with high mortality. In this study, the efficacy of the Eazyplex(R) SuperBug Complete A system (Amplex Diagnostics GmbH, Gars-Bahnhof, Germany), based on loop-mediated isothermal amplification (LAMP), to detect the presence of carbapenemases in Acinetobacter spp. directly from bronchoalveolar lavage samples was assessed, detecting all tested carbapenemases in less than 30 minutes with a sensitivity of 103 CFU/ml.

microbiology↗

bioRxiv2019

Quantifying antibiotic impact on within-host dynamics of extended-spectrum beta-lactamase resistance in hospitalized patients

Antibiotic exposure can perturb the human gut microbiome and cause changes in the within-host abundance of the genetic determinants of drug-resistance in bacteria. Such within-host dynamics are expected to play an important role in mediating the relationship between antibiotic use and persistence of drug-resistance within a host and its prevalence within a population. Developing a quantitative representation of these within-host dynamics is an important step towards a detailed mechanistic understanding of the population-level processes by which antibiotics select for resistance. Here we study extended-spectrum beta-lactamase (ESBL) producing organisms of the Enterobacteriaceae bacterial family. These have been identified as a global public health priority and are resistant to most first-line antibiotics for treatment of Enterobacteriaceae infections. We analyse data from 833 rectal swabs from a prospective longitudinal study in three European countries including 133 ESBL-positive hospitalised patients. Quantitative polymerase chain reaction was used to quantify the abundance of the CTX-M gene family - the most wide-spread ESBL gene family - and the 16S rRNA gene as a proxy for bacterial load. We find strong dynamic heterogeneity in CTX-M abundance that is largely explained by the variable nature of the swab sampling. Using information on time-varying antibiotic treatments, we develop a dynamic Bayesian model to decompose the serial data into observational variation and ecological signal and to quantify the potentially causal antibiotic effects. We find an association of treatment with cefuroxime or ceftriaxone with increased CTX-M abundance (approximately 21% and 10% daily increase, respectively), while treatment with meropenem or piperacillin-tazobactam is associated with decreased CTX-M (approximately 8% daily decrease for both). Despite a potential risk for indirect selection, oral ciprofloxacin is also associated with decreasing CTX-M (approximately 8% decrease per day). Using our dynamic model to make forward stochastic simulations of CTX-M dynamics, we generate testable predictions about antibiotic impacts on duration of carriage. We find that a typical course of cefuroxime or ceftriaxone is expected to more than double a patients carriage duration of CTX-M. A typical course of piperacillin-tazobactam or of meropenem - both options to treat hospital acquired infections (HAI) like pneumonia - would reduce CTX-M carriage time relative to ceftriaxone plus amikacin (also an option to treat HAIs) by about 70%. While most antibiotics showed little association with changes in total bacterial abundance, meropenem and piperacillin-tazobactam were associated with decrease in 16S rRNA abundance (3% and 4% daily decrease, respectively). Our study quantifies antibiotic impacts on within-host resistance abundance and resistance carriage, and informs our understanding of how changes in patterns of antibiotic use will affect the prevalence of resistance. This work also provides an analytical framework that can be used more generally to quantify the antibiotic treatment effects on within-host dynamics of determinants of antibiotic resistance using clinical data.

epidemiology↗

bioRxiv2018

Comparative genomic analysis of the emerging pathogen Streptococcus pseudopneumoniae: novel insights into virulence determinants and identification of a novel species-specific molecular marker

Streptococcus pseudopneumoniae is a close relative of the major human pathogen S. pneumoniae. While initially considered as a commensal species, it has been increasingly associated with lower-respiratory tract infections and high prevalence of antimicrobial resistance (AMR). S. pseudopneumoniae is difficult to identify using traditional typing methods due to similarities with S. pneumoniae and other members of the mitis group (SMG). Using phylogenetic and comparative genomic analyses of SMG genomes, we identified a new molecular marker specific for S. pseudopneumoniae and absent from any other bacterial genome sequenced to date. We found that a large number of known virulence and colonization genes are present in the core S. pseudopneumoniae genome and we reveal the impressive number of known and new surface-exposed proteins encoded by this species. Phylogenetic analyses of S. pseudopneumoniae show that specific clades are associated with allelic variants of core proteins. Resistance to tetracycline and macrolides, the two most common resistances, were encoded by Tn916-like integrating conjugative elements and Mega-2. Overall, we found a tight association of genotypic determinants of AMR as well as phenotypic AMR with a specific lineage of S. pseudopneumoniae. Taken together, our results sheds light on the distribution in S. pseudopneumoniae of genes known to be important during invasive disease and colonization and provide insight into features that could contribute to virulence, colonization and adaptation.\n\nImportanceS. pseudopneumoniae is an overlooked pathogen emerging as the causative agent of lower-respiratory tract infections and associated with chronic obstructive pulmonary disease (COPD) and exacerbation of COPD. However, much remains unknown on its clinical importance and epidemiology, mainly due to the lack of specific means to distinguish it from S. pneumoniae. Here, we provide a new molecular marker entirely specific for S. pseudopneumoniae. Furthermore, our research provides a deep analysis of the presence of virulence and colonization genes, as well as AMR determinants in this species. Our results provide crucial information and pave the way for further studies aiming at understanding the pathogenesis and epidemiology of S. pseudopneumoniae.

microbiology↗